Advances in Dynamic/Adaptive Supramolecular Self‐Assembly: From Molecular Design to Stimuli‐Responsive Control

ABSTRACT

Dynamic/adaptive self‐assembled systems based on reversible non‐covalent or dynamic covalent bonds are a core research direction in supramolecular chemistry and materials science. Dynamic/adaptive self‐assembled systems regulate the interactions between building units via external stimuli, enabling dynamic transformation of self‐assembled structures and reversible regulation of functions. The self‐assembled nanostructures with stimuli‐responsiveness and environmental adaptability, demonstrate great application potential in fields such as smart responsive materials, precision biomedicine, and advanced micro/nano manufacturing. This article provides a systematic review of the research progress in dynamic/adaptive self‐assembly systems, with a focus on the design principles and dynamic regulatory properties of key building blocks, such as organic molecules and biomacromolecules. And dynamic regulation of self‐assembled structures by different external stimuli is discussed. Furthermore, the article explores the applications of these systems in smart devices, controlled drug release, and environmental governance. In addition, computational and theoretical approaches are highlighted as essential tools for understanding and predicting the behavior of these systems. Finally, the article analyzes the core challenges currently faced in this field and offers perspectives on future development directions. The review aims to provide theoretical support and practical guidance for the precise design, structural regulation, and performance optimization of dynamic/adaptive self‐assembly systems.

The article provides a systematic review of the research progress in dynamic/adaptive self‐assembly systems, focusing on the design of molecular building blocks and their dynamic control via external stimuli. Applications in smart materials, drug delivery, and environmental governance are explored. It concludes by analyzing current challenges and future directions to guide the field's development toward precise design and optimization.

1. Introduction

Self‐assembly is a process wherein components spontaneously organize into ordered structures via weak intermolecular interactions, such as hydrogen bonding, host‐guest interactions, van der Waals forces, electrostatic interactions, and π–π stacking [1, 2, 3, 4, 5]. It serves as an important method for preparing functional nanomaterials. A conventional self‐assembly system often leads to static structures that are fixed upon formation. However, the development of smart materials increasingly requires environmental adaptability and tunable functionality. The inherent static nature therefore, severely restricts the applicability and practical scope of traditional self‐assembled systems. For example, conventional self‐assembled systems cannot achieve a series of functions, such as precision drug release, smart switching, structural reconstruction, and functional conversion [6, 7]. These limitations have driven self‐assembly research from pursuing static and stable assembled structures to exploring new dynamic and adaptive functions. In more detail, the self‐assembly process proceeds as follows: initially, building blocks are uniformly dispersed. Upon adjusting external conditions (e.g., temperature, pH, or solvent composition), intermolecular forces guide the molecules to first form small primary aggregates, which then grow and rearrange into ordered supramolecular architectures with defined morphologies. This bottom‐up process is reversible and tunable, allowing precise structural control [8, 9]. This understanding allows researchers to rationally design building blocks and assembly conditions to create nanostructures (e.g., micelles, vesicles, fibers, or sheets) tailored for specific applications. By introducing stimuli‐responsive moieties, the same reversible assembly principles can be exploited for on‐demand drug release, adaptive sensors, and environmental pollutant capture [10, 11].

However, with the advancement of self‐assembly technology, the dynamic and adaptive self‐assembled systems emerged as required. The core mechanism of such systems relies on the ability to precisely modulate the interactions between building units via external stimuli (e.g., light, pH, enzymes, temperature, and guest molecules) [12, 13, 14, 15]. Recent studies have further demonstrated adaptive behaviors under coupled stimuli [16], as well as pH‐ and concentration‐dependent self‐assembly of oligopeptides [17], providing deeper insights into the responsiveness of these systems. This in turn drives the reversible and dynamic evolution of assembled structures, such as assembly and disassembly, crystalline phase transition, pore size modulation, and morphology reconstruction, thereby achieving dynamic regulation and reversible switching of materials functions [18, 19, 20]. For instance, supramolecular polymer systems with photocontrollable morphology have been explored [21], and orthogonal DNA‐based reconfigurable supramolecular polymers enable sophisticated structural switching [22].

Due to the unique dynamic adaptability, environmental adaptability, and intelligent controllability, the self‐assembled nanomaterials have been widely utilized for the applications in the fields of smart devices, precision medicine, and environmental governance [23, 24, 25]. In the biomedical realm, stimuli‐responsive supramolecular biomaterials for cancer theranostics [26], supramolecular self‑assembling platforms for controlled drug release [27], and peptide‐based nanomaterials for antimicrobial and biomedical applications [28] have been developed, further highlighting their potential in precision medicine.

Dynamic/adaptive self‐assembled nanomaterials, which exhibit unique properties such as self‐healing, recyclability, and adaptability, are designed to mimic the intelligence of living organisms, enabling the creation of new materials that can respond to environmental stimuli, and even display lifelike behavior [29, 30, 31, 32, 33]. For instance, Lee and co‐workers reported a kind of supramolecular sheet structures which constructed by charge‐transfer interactions between pyrene and 7,7,8,8‐Tetracyanoquinodimethane (TCNQ) performed specifically disassembled behavior in response to the reducing action of hydrogen sulfide. This system utilizes the metabolic differences of facultative anaerobes under aerobic and anaerobic conditions to achieve selective regulation of bacterial growth. This study explores the bacterial metabolites as triggers to achieve an adaptive response to environmental conditions, providing a novel perspective for the design of targeted antibacterial materials [34]; Manish and co‐workers designed a self‐assembled material based on donor‐acceptor interactions between polyurethane and metal–organic framework (MOF) nanoparticles, successfully fabricating a nanocomposite coating that integrates rapid self‐healing, strong substrate adhesion, and excellent liquid repellency. Furthermore, by exploiting the porosity of MOF nanoparticles in nanocomposites, a fluorine‐free slippery liquid‐infused porous surface was constructed by infusing silicone oil, achieving stable low ice adhesion strength [35].

In the construction of dynamic/adaptive nanomaterials, precisely controlling the building blocks to form desired nanomaterials is one of the important challenges. To develop dynamic building blocks, some functional building blocks, such as functional organic amphiphilic molecules and polymeric polymers, could be introduced into the self‐assembled systems by modulating the internal interactions of the system or applying external stimuli to control the dynamic self‐assembly, which is possible to achieve effective regulation of assembly pathways and final‐state structures [36, 37, 38]. Additional strategies include the use of pH‐responsive peptide hydrogels and light‐responsive molecular motors to achieve dynamic control over assembly [39, 40]. For instance, Fu and co‐workers proposed a light‐driven interfacial self‐assembly strategy, successfully achieving oriented and ordered close‐packed of MOF polyhedral particles to prepare composite films with a Janus structure, containing a MOF monolayer and a polymer layer [41]; Jin and co‐workers designed a kind of rod‐coil amphiphilic molecules whose self‐assembly behavior can be dynamically regulated through charge‐transfer interactions by controlling the intermolecular interaction of the rigid blocks. The addition of TCNQ guides the formation of supramolecular polymers or sheet‐like aggregates, while the introduction of trinitrophenol suppresses assembly via competitive interactions [42]; Liu and co‐workers investigated the self‐assembly behavior of dendronized polymers based on ferrocene units. Upon oxidation, these polymers form positively charged polyelectrolytes, or they can construct supramolecular polymers via host‐guest interactions with β‐cyclodextrin (β‐CD). Both forms are capable to generate nanoassemblies in aqueous solution and can be utilized to encapsulate Rhodamine B [43].

In addition to the above examples, self‐assembled nanomaterials have also shown great promise in other key application areas, including energy harvesting, catalytic activity enhancement, and conductivity. For instance, Lee and co‐workers constructed plasmonic supraballs via self‐assembly of gold nanoparticles, achieving broadband solar energy absorption over 90% for efficient solar energy harvesting [44]. Sun and co‐workers proposed a simple self‐assembly strategy and successfully constructed three types of polyoxometalate‐based supramolecular nanosheets with graphene‐like layered structures. By introducing the surfactant cetyltrimethylammonium bromide as an intercalating agent, they obtained stable and highly active supramolecular nanocatalytic materials [45]. Similarly, hierarchical encapsulation of metal nanoclusters within metal–organic frameworks has also been employed to enhance catalytic performance [46]. Scheiger and co‐workers utilized AI‐driven robotic synthesis to fabricate Cu₃(HTP)₂ MOF thin films with metallic conductivity exceeding 200 S m⁻¹ at room temperature, demonstrating the potential of self‐assembled MOFs in electronic applications [47]. Moreover, photoresponsive supramolecular polymers capable of reversible structural switching [48], as well as a broad range of stimuli‐responsive polymer‐based materials [49] have been reported, further expanding the functional repertoire of self‐assembled systems.

All studies demonstrate that the self‐assembly system is a simple but effective method for constructing functional nanomaterials. By precisely regulating intermolecular interactions and assembly pathways, it produces ordered structures with novel functions. This paves the way for developing a new generation of smart, self‐adaptive, and functionally integrated advanced materials. In this review, we focus on the latest research progress of dynamic and adaptive self‐assembled systems (Figure 1). The regulation types of self‐assembly, core building blocks, and key applications are summarized in detail. We also analyze current challenges and outline future development directions, which will provide an opportunity for broadening the application of dynamic/adaptive self‐assembled systems.

FIGURE 1.

Schematic of dynamic/adaptive self‐assembly system.

2. Building Blocks of Dynamic/Adaptive Self‐Assembly Systems

The design of building blocks is fundamental to achieving dynamic/adaptive self‐assembly. The units must incorporate tunable dynamic interaction sites (e.g., dynamic covalent bonds and non‐covalent interactions) and stimuli‐responsive groups, enabling them to undergo structural transformation and control their assembly behavior under external stimuli [50, 51, 52, 53, 54, 55]. The basic design principles are as follows: (1) introducing stimuli‐responsive moieties into the molecular design; (2) designing stimulus‐sensitive non‐covalent interactions to reversibly switch between assembly and disassembly; (3) altering molecular conformation or the hydrophilic‐hydrophobic balance to change the packing mode; (4) employing reversible covalent reactions or enzymatic reactions to spatiotemporally regulate the assembly pathway. These design principles lay a theoretical foundation for the construction of functional stimuli‐responsive supramolecular systems, and relevant research practices have been carried out to verify their feasibility. A representative example is the work by Lee and co‐workers, who report an environmentally responsive aromatic nanopore system based on precise molecular design [56, 57, 58, 59, 60]. They synthesized a series of rigid‐flexible amphiphilic molecules as building blocks. The aromatic segments drive the self‐assembly of defined nanopores via π–π stacking, while the grafted oligo(ethylene glycol) dendrons act as stimuli‐responsive switches. External stimuli (e.g., temperature, pH) trigger dendron conformational changes, which modulate the intermolecular π–π interactions and induce reversible pore gating or higher‐order structural remodeling (e.g., toroid‐to‐helix transition) without disassembly. This regulation enables the system with dynamic, life‐like functions such as guest pumping and enzyme reaction modulation. To further elaborate on the basis of such dynamic self‐assembly systems, the subsequent content will focus on the core components of self‐assembly building blocks, such as organic molecules, peptides, etc.

2.1. Organic Molecules

Organic molecules used as building blocks discussed here mainly including organic small molecules and macromolecules [36, 61, 62]. The self‐assembly of organic molecules depends on non‐covalent interactions such as hydrogen bonding, π–π interactions, host‐guest interactions, and hydrophilic‐hydrophobic interactions. Through precision engineering of molecular structures and harnessing noncovalent interactions, organic building blocks enable the modulation of interaction strength, directionality, and stimuli‐responsiveness [63]. This facilitates the bottom‐up assembly of supramolecular materials with programmable functions across multiple length scales, from the nano‐ to the macroscale.

Lee and co‐workers construct a self‐assembled sheet system based on rod‐coil aromatic amphiphiles with laterally grafted hydrophilic dendrimer chains, which exhibit temperature‐responsive behavior [64]. When the solution is heated to 42°C, the tightly packed scrolled structure gradually loosens and subsequently transforms into an open sheet due to the dehydration of oligo(oxyethylene) chains (Figure 2a). The most distinctive feature of the rod‐coil molecules studied in this work is their ability to self‐assemble into scrolled sheets with thermally responsive unfolding behavior, which enables the construction of intelligent 2D materials with precisely controllable functions in applications such as energy storage devices with abundant active sites and fast ion diffusion channels, as well as drug delivery vehicles for controlled capture and release, etc. A unique supramolecular tubular bamboo culm structure was also reported, in which the nanotubes can hierarchically self‐assemble into two‐dimensional sheet structures in response to aromatic guest molecules [65]. When trans‐azobenzene is introduced as a guest, the nanotubes assemble into hierarchical sheets via lateral interactions. Under ultraviolet (UV) irradiation, the hierarchical sheet structures disassemble back into the constituent nanotubes due to trans‐cis isomerization. Upon recovery from the cis‐form to the trans‐form of azobenzene, the hierarchical sheet assembly can be re‐induced (Figure 2b). This system exhibits reversible switching between nanotubes and sheets triggered by external stimuli.​

FIGURE 2.

(a) Molecular structures of the rod‐coil molecule and a representation of the dynamic scrolled sheets. Reproduced with permission [Ref 64]. Copyright at 2025 Wiley‐VCH GmbH. (b) Molecule structures and the schematic of the reversible switching between the supramolecular tubular culm and a hierarchical sheet‐assembly, based on a seesaw‐shaped amphiphile. Reproduced with permission [Ref 65]. Copyright at 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular design plays a key role in the regulation of the self‐assembled structure. Nishimura and co‐workers systematically investigated the self‐assembly behavior of four amphiphilic copolymers with distinct chain architectures, namely AB diblock, ABA triblock, three‐arm star block, and cyclic graft copolymers (Figure 3a) [66]. The study demonstrates that variations in macromolecular architecture can lead to the formation of diverse nanostructures, including unilamellar vesicles (Figure 3b), cylindrical micelles (Figure 3c), spherical micelles (Figure 3d), and multilamellar vesicles (Figure 3e). This differentiated self‐assembly behavior primarily originates from distinct folding patterns of the multi‐armed hydrophobic segments, which result in variations in the surface area of the hydrophilic regions within the amphiphilic units of the polymers, ultimately leading to the formation of assemblies with different morphologies. This work elucidates the influence of macromolecular architecture on the self‐assembly behavior of non‐AB‐type amphiphilic copolymers, thereby deepening the current understanding in the field of polymer self‐assembly. Consequently, this research is expected to advance the development of novel design strategies for multi‐arm copolymers, enabling the controlled fabrication of molecular assemblies with well‐defined nanostructures.

FIGURE 3.

(a) Chemical structure of maltopentaose‐b‐PPO (AB block copolymer), maltopentaose‐bPPO‐b‐maltopentaose (ABA block copolymer), 3‐arm maltopentaose‐b‐PPO star copolymer (3‐arm AB block copolymer), and cycloamylose‐g‐PPO (cyclic graft copolymer). SAXS profiles (open circles) of the self‐assembled particles in the (b) AB block copolymer solution, (c) ABA block copolymer solution, (d) 3‐arm AB block copolymer solution, and (e) cyclic graft copolymer solution. The red solid lines show the theoretical curves obtained using (b)bilayer cross‐sectional, (c) core–shell cylinder, (d) core–shell sphere, and (e) weakly ordered membrane‐stack‐particle models. Reproduced with permission [Ref 66]. Copyright at 2023 The Royal Society of Chemistry.

2.2. Macrocyclic Host Molecules

Macrocyclic host molecules, such as cyclodextrins, crown ethers, calixarenes, pillararenes, and cucurbiturils, have become essential building blocks in supramolecular chemistry due to their unique cavity structures, modifiable chemical properties, and excellent host‐guest recognition capabilities [67, 68, 69, 70, 71]. Through precise molecular recognition and dynamic reversible noncovalent interactions (e. g., hydrophobic effects, hydrogen bonding, π–π stacking, and metal coordination), these molecules effectively guide and regulate molecular assembly processes [72, 73, 74, 75]. This enables the construction of diverse supramolecular architectures ranging from discrete host‐guest complexes to multidimensional ordered assemblies like vesicles, gels, and framework materials. These assemblies not only exhibit intelligent characteristics such as stimulus responsiveness, self‐healing, and adaptability but also hold broad application prospects in fields such as drug delivery, chemical sensing, environmental remediation, and biomimetic catalysis [76, 77, 78, 79]. For example, hybrid systems based on cyclodextrin‐pillararene structures can be used for the removal of pollutants from water, while cucurbituril‐mediated self‐assembled colloids show significant potential in controlled drug release and catalysis [80, 81, 82]. Such research not only deepens the understanding of intermolecular interactions and self‐assembly mechanisms, but also provides a robust molecular platform for designing novel functional materials.

Fan and co‐workers constructed a redox‐responsive self‐assembly system based on a ferrocene (Fc)‐containing β‐cyclodextrin (β‐CD) derivative (βCD‐EG‐Fc) [83]. Driven by host‐guest recognition between the β‐CD and Fc moiety, βCD‐EG‐Fc initially formed network‐like structures. After aging, these structures transformed into vesicles, a process primarily mediated by hydrogen bonding. In contrast, the oxidized form (βCD‐EG‐Fc⁺) self‐assembled into cationic vesicles in the absence of host‐guest complexation. By controlling Fc/Fc⁺ redox reactions, reversible aggregate transformation was achieved (Figure 4a). The study provides deeper insight into redox‐responsive β‐CD/Fc self‐assemblies and contributes significantly to the development of a single‐component host‐guest inclusion model. Yang and co‐workers successfully constructed a metallosupramolecular polymer (DSPy⊂SHP5@Zn) through the hierarchical self‐assembly of a dual‐site pillar[5]arene host (SHP5), a ditopic guest molecule (DSPy), and Zn^{2 +} ions, depending on host‐guest recognition and metal‐ligand coordination interactions [84]. Benefiting from the reversible nature of dynamic covalent and noncovalent interactions, the DSPy⊂SHP5@Zn assembly forms a supramolecular gel. This gel exhibits excellent sol‐gel transition in response to heat, redox reactions, pH changes, and competitive guests (Figure 4b). The study provides a simple and efficient method for constructing multi‐stimuli‐responsive smart gels, offering promising potential for expanding the research scope and applications of intelligent supramolecular materials.

FIGURE 4.

(a) Schematic illustration of the redox‐responsive self‐assembly in the bCD‐EG‐Fc system. Reproduced with permission [Ref 83]. Copyright at 2020 The Royal Society of Chemistry. (b) The multi‐stimuli‐responsive‐properties of the metallosupramolecular gel DSPy⊂SHP5@Zn‐G triggered by different stimuli. Reproduced with permission [Ref 84]. Copyright at 2023 The Royal Society of Chemistry.

Wang and co‐workers report the regulation of fluorescence and self‐assembly in a salicylaldehyde azine‐containing bola‐amphiphile G via host‐guest interactions with water‐soluble pillar[5]arene (WP5) [85]. By adding varying amounts of WP5, the fluorescence properties and self‐assembled aggregates of G can be precisely regulated. Furthermore, the emission and self‐assembly behavior of the G‐WP5 system can be modulated by changing the pH (Figure 5). This fluorescence regulation strategy holds significant promise for the construction of advanced fluorescent organic materials.

FIGURE 5.

(a) Chemical structures of G, WP5, and MG; (b) Cartoon representation of the regulation of fluorescence and self‐assembly of G by WP5 and pH conditions. Reproduced with permission [Ref 85]. Copyright at 2024 Wiley‐VCH GmbH.

2.3. Biomacromolecules

Biomacromolecules (e.g., DNA, RNA, proteins, and peptides) are used as building blocks for supramolecular self‐assembly due to their precise sequence encoding capability. They offer precise sequence encoding, predetermined high‐order structures, and inherent structure‐function integration refined by biological evolution [86, 87, 88]. These characteristics enable biomacromolecules to achieve complex programmable assembly far beyond traditional molecules, and to endow self‐assembled materials with advanced functionalities, including dynamic responsiveness, efficient catalysis, and information transfer [89, 90, 91]. Among them, peptides act as a class of high‐performance assembly units due to their programmable amino acid sequences, diverse side‐chain groups, and tunable molecular conformations [92, 93, 94].

Bao and co‐workers successfully designed a pH‐responsive peptide molecule and incorporated it into a PNIPAM polymer network to construct hydrogel actuators [95]. Based on the assembly and disassembly of the peptide molecules under different pH conditions, bilayer and heterogeneous hydrogel actuators were fabricated (Figure 6a). The controllable and reversible self‐assembly and disassembly processes of the peptide molecules can regulate the volume swelling of the PNIPAM‐peptide composite hydrogels. This provides the driving force to deformation and actuation in the heterogeneous hydrogels. Wang and co‐workers effectively regulated the self‐assembly and disassembly processes of the designed short β‐sheet peptide IIIGGHK through variations in concentration, pH, and mechanical agitation [96]. They used microscopic imaging, neutron scattering, and infrared spectroscopy to monitor the interconversion between thin left‐handed protofibrils and higher‐order right‐handed nanotubes (Figure 6b). These controlled disassembly processes arise primarily from the fact that specific histidine‐histidine interactions between protofibrils are responsive to the above stimuli. The self‐assembly and disassembly characteristics of the peptide enabled the encapsulation and stimulus‐triggered rapid release of the hydrophobic drug curcumin.

FIGURE 6.

(a) Reversible and pH‐responsive self‐assembly of peptides, and the reversible macroscopic shape deformation of a bilayer hydrogel in response to pH change. Reproduced with permission [Ref 95]. Copyright at 2023 Wiley‐VCH GmbH. (b) The self‐assembly and disassembly of the short β‐sheet peptide IIIGGHK under various stimuli. Reproduced with permission [Ref 96]. Copyright at 2024 American Chemical Society.

3. Regulation Types of Dynamic/Adaptive Self‐Assembly Systems

The key principle of dynamic/adaptive self‐assembly systems relies on the reversible regulation of their functions through structural changes driven by external stimuli. External stimuli modulate the dynamic equilibrium of interactions between building units by changing their chemical or physical properties, thereby driving the structural reconstruction of the assembly and ultimately achieving precise functional control [97, 98, 99, 100, 101].

3.1. Regulation by Light

Light responsiveness is one of the most promising regulation strategies in dynamic self‐assembly systems. It offers distinct advantages such as rapid response, high spatiotemporal resolution, non‐invasiveness, and remote controllability [102]. Illumination at specific wavelengths can trigger isomerization in the photo‐responsive moieties of building units, such as cis‐trans or ring‐opening/closure isomerization. This molecular change modifies their physicochemical properties, which in turn regulate intermolecular interactions. Consequently, the assembly undergoes structural reconfiguration, achieving reversible and dynamic control over its functionality.

Selectively regulating the bioactivity of antimicrobial peptides is not only a fascinating scientific challenge but also an urgent requirement in the field of localized antibacterial therapy. Li and co‐workers constructed a smart antibacterial system via host‐guest driven dynamic self‐assembly between branched cyclodextrins and cationic linear peptides grafted with azobenzene side chains (Figure 7a). The self‐assembled structure can be reversibly regulated through photoresponsive isomerization of azobenzene moieties [103]. The trans‐azobenzene side chains on the cationic peptides can interact with branched cyclodextrins to form microscale sheet‐like structures with high surface potentials. The multivalent positive charges on these sheet surfaces endow the system with antibacterial properties. However, UV‐triggered cis‐isomerization of azobenzene moieties weakens the host‐guest interactions between azobenzene and branched cyclodextrins, driving the system to transform into small, inactive nanospheres (Figure 7b). Thus, light regulation enables selective switching of antibacterial activity. This photoresponsive peptide self‐assembly system with switchable bioactivity is expected to provide novel insights into the development of smart supramolecular antibacterial materials. Lee and co‐workers reported a spontaneous chirality induction phenomenon in a single‐layer 2D network structure formed by the self‐assembly of tetrapod azobenzene molecules [104]. The protruded azobenzene units inside the channels undergo selective isomerization under UV irradiation, leading to reversible deformation of the chiral channels while maintaining the 2D framework stability (Figure 7c). The chiral network can selectively capture one enantiomer from a racemic solution and release triggered by light (Figure 7d). This discovery lays a foundation for constructing 2D chiral networks with complex channel functions, such as capable of being selective encapsulation, delivery, and subsequent release.

FIGURE 7.

(a) Structures of peptides P1‐P5 and the tri‐β‐CD. (b) The schematic drawing of the photoresponsive assembly between P1 and tri‐β‐CD. Reproduced with permission [Ref 103]. Copyright at 2021 Chinese Chemical Society. (c) Molecular structure and switchable cavities with selective isomerization upon UV irradiation, (d) schematic representation of the enantioselective encapsulation from a racemate and then release triggered by UV irradiation. Reproduced with permission [Ref 104]. Copyright at 2023 Wiley‐VCH.

Li and co‐workers constructed a dynamic self‐assembled system, which is regulated by light based on anionic polyoxometalates and cationic azobenzene‐peptide conjugates [105]. The non‐equilibrium 2D nanosheets are maintained only by UV‐driven trans‐to‐cis isomerization of azobenzene, otherwise, it collapses to a globular state. This work provides a new strategy for constructing light‐driven dynamic two‐dimensional self‐assemblies and broadens the research scope of photo‐responsive peptide‐based supramolecular systems (Figure 8a). Sun and co‐workers designed and synthesized a pair of azobenzene‐bridged bis‐tryptophan enantiomers [106]. Driven by proton release during the hydrolysis of glucono‐δ‐lactone, their alkaline solution self‐assembled into helical structures of opposite chirality, exhibiting strong and mirror‐imaged circular dichroism signals (figure 8b). Upon UV‐induced trans‐ to cis‐isomerization of the azobenzene moiety, the chiral helical structures transformed into CD‐silent nanoparticles (Figure 8c). Importantly, the system allows intelligent and reversible switching between chiral amplification and signal silencing triggered by irradiation at different wavelengths, realizing a photo‐controlled chiroptical switch. These studies collectively reveal that photo‐responsive self‐assembly is evolving from passive response to active adaptation, shifting from constructing static structures to regulating dynamic processes. Through deep integration of photochemistry, supramolecular chemistry, and systems science, it is promising to create next‐generation adaptive intelligent material systems capable of environmental adaptation, and information processing.

FIGURE 8.

(a) Schematics of the molecular components and their co‐assembly, and corresponding photo‐switchable and dynamic 2D nanosheet. Reproduced with permission [Ref 105]. Copyright at 2020 The Royal Society of Chemistry. (b) The representation of a photocontrolled chiroptical switch, (c) Schematic presentation of Azo‐di‐D/L‐Trp and their photoswitchable chiral self‐assembly behaviors. Reproduced with permission [Ref 106]. Copyright at 2024 Elsevier Inc.

3.2. Regulation by Temperature

Temperature is one of the most general and controllable physical stimuli in nature. It provides a unique driving force for the dynamic self‐assembly of smart materials, and has potential applications in smart materials, biomedical engineering, and environmental engineering [107, 108]. Temperature regulation of dynamic self‐assembly systems depends on controlling non‐covalent interactions or affecting the conformation and solubility of assembly units, thereby breaking thermodynamic equilibrium and driving the system to a new equilibrium state [109]. The key mechanisms of thermal responsive can be considered that temperature affects the hydrophobic interactions between the building blocks. For amphiphilic molecules containing both hydrophobic and hydrophilic segments (e.g., block copolymers, amphiphilic organic molecules), the increase in temperature breaks the hydrogen bonds between the hydrophilic segments and water molecules [110]. This process is enhances hydrophobic interactions, driving spontaneous aggregation structures such as micelles, vesicles, or gels. Conversely, upon cooling, the weakened hydrophobic interactions lead to the disassembly of these structures, causing the molecules to redisperse into the aqueous solution.

Lee and coworkers have successfully synthesized macrocyclic amphiphiles composed of planar aromatic macrocyclic segments and hydrophilic dendritic molecules [111]. The macrocyclic molecules self‐assemble into two‐dimensional sheet‐like structures in aqueous solution. Upon heating‐cooling cycles, the planar sheets undergo reversible splitting, transforming into elongated nanofibers (Figure 9a). The dynamic switching behavior arises from the thermally induced dehydration of the oligoether dendritic chains, which shifts their local environment from hydrophilic to hydrophobic, thereby driving the structural transformation. This unique supramolecular behavior exhibits reversible conversion into smaller nanostructures in response to external stimuli. Such behavior may offer a novel strategy for the rational design and synthesis of intelligent aqueous materials. In addition to the dynamic sheet structures, they also reported the temperature‐regulated self‐assembly system of reversible helical supramolecular polymerization of stacked toroidal structures. These structures can maintain tubular architectures in aqueous solution [112]. At room temperature, these tubular structures are composed of discrete stacked toroidal structures with a hydrophobic interior. Upon heating, the tubular structures based on stacked toroids undergo reversible helical supramolecular polymerization, transforming into helical tubular structures through the interconnection between spirally open toroids (Figure 9b). The helical polymerization originates from the tilting transition of closed toroidal structures driven by the thermal dehydration of hydrophilic oligoether dendrons surrounding the toroidal frameworks. As a result, the closed toroids transform into spirally open toroids. This unique tubular wall structure will provide an opportunity to explore temperature‐responsive nanoreactors for chemical transformations, benefiting from its distinct spatial confinement effects. Koga and co‐workers reported a study on the precise regulation of amino acid‐based vinyl polymers based on temperature [113]. In this system, the researchers designed and synthesized a water‐soluble polymer via controlled polymerization techniques. The polymer block sequence was engineered to exhibit a gradient thermo‐responsive behavior along the polymer chain. The underlying mechanism due to the temperature‐dependent, gradual modulation of the hydrophilic/hydrophobic balance of different segments, which drives the polymer to undergo complex, multi‐step self‐assembly. Specifically, upon heating (4°C→20°C→70°C), the system sequentially transitions from a soluble state to spherical micelles and then to vesicles, representing a process of ordering. Conversely, during cooling (70°C→20°C→4°C), a hysteretic pathway is observed, where the vesicles transform into wormlike micelles as an intermediate state before finally disassembling back into the soluble form (Figure 9c). The temperature‐responsive behavior of this material surpasses the simple assembly/disassembly switch mode, enabling reversible, multi‐step transformations among various nanostructures, including spherical micelles, wormlike micelles, and vesicles. This study provides a novel design concept for developing high‐performance, multifunctional responsive self‐assembled nanomaterials required for next‐generation biomedical applications.

FIGURE 9.

(a) Molecule structure and schematic representation of the formation of the 2‐D sheet that undergoes reversible break‐up into nanofibers. Reproduced with permission [Ref 111]. Copyright at 2021 Royal Society of Chemistry. (b) Molecular structure of amphiphile molecule and schematic representation of reversible helical polymerization of tubule stacked by toroid with rapid response to heating‐cooling treatments. Reproduced with permission [Ref 112]. Copyright at 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. (c) Chemical structure of the sequence‐controlled amino acid‐derived vinyl polymer and their dynamic self‐assembled strecture tirgered by temperature. Reproduced with permission [Ref 113]. Copyright at 2020 American Chemical Society.

3.3. Regulation by pH

pH‐responsive regulation self‐assembly behavior based on the changing in hydrogen ion concentration in the assembly environment, is widely present in organisms and serves as an ideal regulatory method for biomedical applications. The regulation mechanism is as follows: the change in pH triggers the protonation or deprotonation of pH‐sensitive groups (e.g., carboxyl groups, amino groups, hydrazone bonds, imine bonds, etc.) in the building blocks, which alter the charge properties of the molecules and their hydrogen bond donor/acceptor abilities [114, 115, 116, 117]. This further modulates the balance between electrostatic and hydrogen‐bond interactions among the building blocks, which drives the dynamic evolution of the assembly structures, manifested in processes such as gel‐sol transition, channel opening/closing, and morphological changes [118, 119, 120]. Consequently, it enables the reversible regulation of the self‐assembly's functions.

De and co‐workers reported a study on the coassembly of hydrophobic coumarin‐integrated cationic copolymers and anionic copolymers [121]. In aqueous medium at pH 7.4, the two copolymers coassemble to form vesicles with electrically neutral zwitterionic surfaces. When the solution pH is varied, a charge‐switchable behavior (positive to neutral to negative) is observed, and the vesicles undergo a significant morphological transition into spherical aggregates (Figure 10a). At pH 7.4, the coassembled vesicles possess neutral surface charges and can resist the adsorption of nonspecific proteins (pepsin and lysozyme) through electrostatic repulsion. In addition, the bilayer membrane of the vesicles can encapsulate both hydrophilic and hydrophobic guest molecules and achieve sustained release in the presence of 10 mm esterase; the zwitterionic vesicles constructed in this study exhibit resistance to nonspecific proteins and efficient encapsulation and release capabilities for small molecules, indicating that this coassembly system has potential application value as a drug delivery vehicle. Lee and co‐workers reported that aromatic amphiphiles based on cruciform aromatic segments self‐assemble into 2D sheet structures in aqueous environments, which perform fluorescence‐switchable behavior triggered by pH [122]. These sheet structures exhibit strong excimer emission under neutral pH conditions. When the pH decreases, the pyridine units in the aromatic moieties are protonated, leading to loose packing of pyrene units and quenching of excimer emission. However, when the pH is restored to neutrality, the pyridine units are deprotonated, the pyrene units pack tightly again, and the excimer emission can be fully recovered, indicating a completely reversible fluorescence emission switching property (Figure 10b). The fluorescence sheets can serve as an ideal fluorescence sensor for the detection of acidic substances in aqueous environments.

FIGURE 10.

(a) Schematic representation of coassembly triggered by Reproduced with permission [Ref 121]. Copyright at 2024 American Chemical Society. (b) Depiction of the single‐layered sheet structure and schematic representation of fluorescence emission on/off switching mechanism. Reproduced with permission [Ref 122]. Copyright at 2025 The Royal Society of Chemistry.

pH‐responsive DNA assemblies have attracted increasing attention due to their great application potential in diverse fields. Yang and co‐workers proposed a reversible pH‐responsive DNA assembly strategy at room temperature based on the zwitterion glycine betaine (GB) serving as a charge‐regulating molecule [123]. The reversible assembly and disassembly of DNA nanostructures can be achieved by alternately modulating acidic and alkaline environments (Figure 11a). Under acidic conditions, the carboxylate groups in GB undergo protonation, rendering the molecules positively charged overall, which in turn effectively shields the inherent electrostatic repulsion of DNA strands. Molecular simulation results indicate that the newly formed carboxyl groups in protonated GB can form hydrogen bonds with DNA bases, thereby facilitating the assembly process of DNA strands. In alkaline solutions, the carboxylate groups in GB are deprotonated, and the molecules regain electrical neutrality, thus inducing the dissociation of DNA assemblies. Wang and co‐workers designed a novel anticancer prodrug molecule FA‐EEYSV‐NH₂, which consists of a targeting unit (folic acid, FA), a dipeptide linker, and a therapeutic peptide segment [124]. This molecule self‐assembles into nanoparticles at pH 7.0 and transforms into nanofibers at pH 5.0 (Figure 11b). The pH‐responsive property allowed the self‐assemblies to be deployed as targeted self‐delivery carriers for the prodrug.

FIGURE 11.

(a) Schematic illustration of pH‐responsive reversible DNA self‐assembly. Reproduced with permission [Ref 123]. Copyright at 2020 Jilin University, The Editorial Department of Chemical Research in Chinese Universities, and Springer‐Verlag GmbH. (b) Molecular structure and the pH‐triggered transformation from nanoparticles to nanofibers. Reproduced with permission [Ref 124]. Copyright at 2021 American Chemical Society.

3.4. Regulation by Guest Molecule

Guest molecules precisely regulate the structural formation, dynamic transformation, and functional expression of assemblies through reversible non‐covalent interactions with host assembly building blocks. In supramolecular dynamic self‐assembly systems, guest molecules can bind to specific recognition sites of host molecules in a targeted manner based on hydrogen bonding, hydrophobic interactions, electrostatic interactions, or specific host‐guest recognition (e.g., recognition pairs including crown ether‐ammonium ion, cyclodextrin‐alkyl chain, and cucurbituril‐aromatic group) [125, 126]. The binding induces conformational rearrangement or intermolecular cross‐linking of host building blocks, thereby driving the transition from a disordered molecular dispersion state to an ordered nanoscale assembled state (e.g., fibers, vesicles, and sheet‐like aggregates) [127, 128]. The driving effect exhibits distinct dynamic reversibility. When external environmental conditions (e.g., pH, temperature, and ionic strength) change or competitive guest molecules are introduced, the original host‐guest interactions dissociate, triggering the reconstruction of the spatial arrangement of host building blocks [129, 130]. Consequently, the assemblies undergo disassembly or transformation into new assembled states, enabling the cyclic regulation of the assembly‐disassembly‐reassembly process.

Lee and co‐workers reported a switchable supramolecular chiral 2D material constructed on the basis of donor‐acceptor interactions between a pyrene‐based amphiphile and 7,7,8,8‐tetracyanoquinodimethane (TCNQ) (Figure 12a) [131]. When TCNQ is irreversibly photoreduced to its anionic form, the supramolecular chiral sheets spontaneously disassemble. In contrast, the subsequent addition of TCNQ can drive the disassembled molecules to reassemble and repeatedly forming optically active sheet structures (Figure 12b). This phenomenon demonstrates that the assembled material exists only transiently under the condition of continuous TCNQ supply. Liu and co‐workers designed a dynamically reversible 2D protein assembly system based on host‐guest interactions [132]. The system is driven by supramolecular interactions between cucurbit[8]uril (CB[8]) and a designed guest‐functionalized protein (SP1S98C‐MMV⁺). This assembly can be triggered to disassemble upon the introduction of the competitive guest molecule FGG. Furthermore, reassembly can be achieved by dialysis followed by re‐introducing the linker CB[8], resulting in highly ordered, single‐layer‐like 2D nanoarrays (Figure 12c). This assembly‐disassembly‐reassembly behavior endows the 2D protein nano‐platform with great potential for constructing more extended and complex systems.

FIGURE 12.

(a) Molecular structures of the amphiphile molecule and TCNQ. (b) Schematic representation of a TCNQ‐driven switchable chiral sheet showing CPL. Reproduced with permission [Ref 131]. Copyright at 2023 Wiley Periodicals LLC. (c) Schematic representation of the host‐guest induced assembly of 2D protein nanosheets and the FGG‐triggered disassembly process. Reproduced with permission [Ref 132]. Copyright at 2021 The Royal Society of Chemistry.

Zhao and co‐workers designed and prepared amphiphilic 18‐PDIiol conjugates composed of hydrophobic isooctyl‐perylenebisdiimide and hydrophilic DNA sequences [133]. Driven by the strong π–π interactions of the PDI moieties, the amphiphilic D18‐PDIiol molecules can self‐assemble into spherical micelles in aqueous solution. When an excess of β‐cyclodextrin (β‐CD) or α‐cyclodextrin (α‐CD) is added to the system, the spherical micelles are transformed into nanofibers; subsequently, upon the addition of the competitive guest molecule AMA, which has a high binding constant to β‐CD, the nanofibers can reversibly transform back into spherical micelles (Figure 13a). This assembly morphology regulation strategy based on host‐guest chemistry holds promising potential applications in related fields such as bioimaging and drug delivery. Based on the host‐guest complexation strategy, Zhang and co‐workers reported a novel supramolecularly activatable photosensitizer [134]. This system employs cucurbit[7]uril (CB[7]) to regulate the aggregate and monomer states of a thio‐pentamethine cyanine dye bearing α‐naphthyl groups on its side chains (Naph‐α‐TCy5), enabling the on‐off switching of its photosensitizing activity. After Naph‐α‐TCy5 undergoes host‐guest complexation with cucurbit[7]uril (CB[7]), the resulting host‐guest complex (Naph‐α‐TCy5‐CB[7]) is converted into a supramolecularly caged photosensitizer. When a competitive guest with a stronger binding affinity to CB[7] is introduced into the system, Naph‐α‐TCy5 can be released from the cavity of CB[7] via competitive host‐guest complexation and recover its self‐assembled aggregate state (Figure 13b). Based on this switching mechanism, Naph‐α‐TCy5‐CB[7] can be in situ activated by polyamines in cancer cells, ultimately realizing highly efficient photodynamic therapy with high specificity and excellent biocompatibility.

FIGURE 13.

(a) The self‐assembly of D18‐PDIiol conjugates and their stimuli‐responsiveness based on the host‐guest interaction. Reproduced with permission [Ref 133]. Copyright at 2023 The Royal Society of Chemistry. (b) Schematic presentation of a supramolecularly activatable photosensitizer design with Naph‐α‐TCy5 and CB[7]. Reproduced with permission [Ref 134]. Copyright at 2025 Chinese Chemical Society.

3.5. Regulation by Metal‐Ligand Coordination

Metal‐ligand coordination is a class of non‐covalent interactions characterized by directionality, reversibility, and tunability, serving as a key driving force for constructing dynamic self‐assembling supramolecular systems [135, 136]. Metal‐ligand coordination endows self‐assemblies with multiple stimulus‐responsive capabilities. For example, controlled structural transitions of the assembled systems can be achieved by altering temperature, adding competing ligands, adjusting pH, or applying redox stimuli [137, 138]. This inherent dynamic reversibility enables metal‐coordination‐driven supramolecular materials to mimic the adaptability and reconfigurability of biological systems. For example, they can undergoing component exchange or topological transformation upon chemical stimuli, or exhibiting out‐of‐equilibrium adaptive behaviors in response to external energy input [139, 140].

Plajer and co‐workers provide a typical example of metal‐coordination‐driven supramolecular dynamic self‐assembly. They started with the bond types involved in monomer assembly (Figure 14a) and proposed a hypothesis regarding the stacking behavior of zinc(II) Salphen complexes (Figure 14b) [141]. On this basis, by exploiting the directionality, reversibility, and tunability of metal‑ligand bonds, they discovered that modulating the ligand structure can direct the assembly process toward either thermodynamic or kinetic pathways, thereby establishing a key principle (Figure 14c). Furthermore, they leveraged metal‐ligand exchange reactions to achieve dynamic control over gelation and luminescence. This finding advanced supramolecular chemistry from static design to process control. Inspired by this, they introduced the novel concept of “structural water as a comonomer” [142]. In contrast to conventional self‐assembly driven by the hydrophobic effect, zinc(II) complexes assemble in water into supramolecular fibres through the inclusion of structural water (Figure 14d). Single‐crystal X‐ray diffraction directly confirmed that the complex forms a solid‐state polymer via water inclusion (Figure 14e). Cryo‐TEM images clearly show the nanofibers formed in a 1 mm aqueous solution of A^°, and the embedded gray‐value profile further supports the hollow structure (Figure 14f). High‐resolution magic‐angle spinning diffusion‐ordered spectroscopy (HR‐MAS DOSY) indicates that 30 mm A^° in D₂O exhibits a single diffusion component, confirming the homogeneity of the fibrous structure (Figure 14g). These structurally water‐stabilized hollow nanofiber hydrogels display adaptive properties such as thermomechanical responsiveness, chemically triggered disassembly, and chiral recognition, demonstrating that dynamic reconfigurability not only arises from the reversibility of metal‐ligand bonds but can also be extended to the cooperative involvement of solvent molecules. Collectively, these works illustrate the controllability, adaptability, and reconfigurability of supramolecular systems endowed by the dynamic reversibility of metal‐coordination bonds, from the perspectives of precise assembly pathway control and synergistic solvent molecule participation.

FIGURE 14.

(a) Outset of bond types constructing monomers for self‐assembly. (b) Hypothesis outlined in the literature of Zinc(II) Salphen complexes undergoing stacking. (c) Key concepts established in this contribution arising from the bond type characteristics. M = metal, L = ligand, R = alkyl chain. Reproduced with permission [Ref 141]. Copyright at 2025 Wiley‐VCH GmbH. (d) Self‐assembly in water driven by the hydrophobic effect versus Ao assembling into supramolecular fibres by inclusion of structural water. (e) Single‐crystal X‐ray diffraction structure of zinc(II) complex assembling into a solid‐state polymer via water inclusion. (f) Cryo‐TEM image of 1 mm aqueous solution of A^o with an inlay of gray value profile plot. (g) Stacked HR‐MAS DOSY (400 MHz, D₂O, 25°C) spectrum of Ao (30 mm) measured at a diffusion time of 0.5 s. Reproduced with permission [Ref 142]. Copyright at 2026 Wiley‐VCH GmbH.

4. The Applications of Dynamic/Adaptive Self‐Assembly

Dynamic/adaptive self‐assembly represents a paradigm shift in materials science from traditional static constructs toward intelligent systems. The materials can mimic the key characteristics of living systems by actively sensing environmental changes, such as temperature, pH, light, or specific biological signals, and responding with real‐time, reversible adjustments in their structure, morphology, and even function [143, 144]. This stimuli‐responsive adaptive capability is driving broad technological innovation, spanning from the nano‐ and micro‐scale up to macroscopic functional devices. Dynamic self‐assembly has demonstrated significant applications across multiple fields [145, 146]. For example, in biomedicine, it has enabled intelligent targeted delivery and dynamic tissue repair [147]. Within smart materials and soft robotics, it has driven the emergence of muscle‐like flexible actuation materials [148]. Moreover, in areas including intelligent nanodevices, adaptive catalysis, self‐healing energy materials, and environmental remediation, it has made possible the construction of reconfigurable optical devices, highly efficient adaptive catalysts, and self‐repairing electrode materials [149, 150]. In this review, we mainly discuss the applications in the fields of smart devices, drug delivery systems, and Environmental governance.

4.1. Smart Devices System

In the field of smart device system, dynamic self‐assembly technology provides a core implementation pathway for the on‐demand regulation of device performance. Tang and co‐workers utilized dye‐sensitized titanium dioxide colloidal microspheres, leveraging their differential absorption and refraction of red and blue light to convert optical energy into chemical flow fields that drive directional particle motion [151]. By programming the angles and intensity ratios of multiple visible light beams, it was possible to construct around the particles a variety of symmetric and intensity‐tunable equivalent potential fields. This enabled the remote and reversible manipulation of the active colloidal system to self‐assemble into five distinct two‐dimensional Bravais lattices (Figure 15a). Ultimately, by dynamically reconfiguring the colloidal crystal through changes in the programming light patterns and observing real‐time alterations in its diffraction patterns of infrared laser light, the study successfully demonstrated a prototype of a reconfigurable photonic device whose performance can be dynamically programmed and tuned in real time using light. Li and co‐workers reported the design and synthesis of a water‐soluble luminescent radical, TTM‐3IMB, which spontaneously assembles with cucurbit[8]uril in aqueous solution to form a well‐defined, dynamically reversible two‐dimensional honeycomb supramolecular organic framework (Figure 15b) [152]. The reversible assembly and disassembly of the framework were observed by temperature‐dependent fluorescence and EPR spectroscopy upon heating‐cooling cycle (Figure 15c–e). The reversibility enables the modulation of spin‐spin interactions and excited‐state dynamics within the framework. The supramolecular organic framework architecture not only enhances the photostability of TTM‐3IMB by fourfold but also increases its photoluminescence quantum efficiency from 2.0% to 5.0%. This work represents a significant step toward tunable optoelectronic, magnetic, and bioresponsive materials.

FIGURE 15.

(a) Simulation and experimental results of the polymorphism with different potential distributions. Reproduced with permission [Ref 151]. Copyright at 2024 Elsevier Inc. (b) Molecular structures of TTM, TTM‐3IMB, and TTM‐3IMB@CB[8]. (c) EPR spectra of TTM‐3IMB@CB[8] before and after heating. (d) PL spectra of TTM‐3IMB@CB[8] with gradual heating to 90°C. (e) PL spectra of TTM‐3IMB@CB[8] with gradual cooling to room temperature. Reproduced with permission [Ref 152]. Copyright at 2025 Wiley‐VCH GmbH.

4.2. Drug Delivery

Dynamic supramolecular self‐assembly systems have emerged as a promising frontier in drug delivery research in recent years. Their core principle depends on leveraging the reversibility and environmental responsiveness of non‐covalent interactions (e.g., hydrogen bonding, hydrophobic interactions, π–π stacking, etc.) to construct delivery carriers capable of intelligently regulating drug release in response to physiological or pathological signals [153, 154]. By mimicking self‐assembly mechanisms in biological systems (e.g., protein folding, membrane formation, etc.), these systems achieve dynamically tunable carrier structures, multifunctionality, and high biocompatibility, demonstrating unique advantages in enhancing drug targeting and reducing side effects [10, 155].

Ye and co‐workers designed a dual‐stimuli‐responsive prodrug molecule, P‐CyPt, which achieves a precise delivery logic involving stimulus‐triggered self‐assembly for tumor accumulation, followed by a second stimulus‐triggered disassembly for drug release [156]. Specifically, upon reaching the tumor tissue, the prodrug first responds to the elevated alkaline phosphatase in the extracellular environment, undergoing in situ self‐assembly into nanoscale aggregates. This effectively traps and retains the drug within the tumor region, enabling initial targeting and accumulation. Subsequently, following cellular internalization, the high intracellular concentration of glutathione acts as a second stimulus. This triggers the disassembly of the nanoscale aggregates and cleaves the prodrug linker, thereby releasing the active cisplatin (Figure 16). This leads to the burst release of active cisplatin, thereby efficiently killing tumor cells. This strategy ingeniously integrates the advantages of tumor enrichment offered by in situ self‐assembly with the controllable release achieved through intracellular disassembly, notably enhancing the therapeutic efficacy of cisplatin while reducing its systemic toxicity.

FIGURE 16.

General design and proposed mechanism of P‐CyPt for cancer theranostics. Reproduced with permission [Ref 156]. Copyright at 2023 Springer Nature Limited.

Tian and co‐workers designed and constructed an intelligent targeted delivery system based on host‐guest interactions [157]. This system employs active targeting β‐cyclodextrin‐modified hyaluronic acid and an anticancer drug conjugate (curcumin‐oxoplatin) as fundamental building blocks. The curcumin guest molecule is specifically encapsulated within the cyclodextrin cavity. The host‐guest inclusion drives the self‐assembly into a well‐defined nanostructure, which not only achieves high drug loading but also exhibits dual‐responsive drug release triggered by the acidic tumor microenvironment and intracellular esterase (Figure 17). This work validates a highly targeted and biosafe delivery platform. More importantly, its ingenious integrated design represents a significant step toward the development of multifunctional, next‐generation anticancer drug delivery systems.

FIGURE 17.

Construction of supramolecular self‐assemblies, HCPNs, and their drug release behaviors. Reproduced with permission [Ref 157]. Copyright at 2020 Elsevier Ltd.

4.3. Environmental Governance

The dynamic reversibility, directionality, and stimulus‐responsive properties of metal‐coordination bonds endow self‐assembled supramolecular nanomaterials with unique advantages in the field of environmental governance [11, 158]. For example, through rational design of ligand structures, metal‐coordination‐driven supramolecular self‐assembling systems can serve as efficient adsorbents, utilizing their three‐dimensional network architecture and abundant metal coordination sites to selectively capture heavy metal ions or organic dye pollutants from water [159, 160]. These dynamic reconfigurable properties endow self‐assembled nanomaterials not only with high removal efficiency but also with advantages, including recyclability, low energy consumption, and smart responsiveness in environmental remediation, offering new insights for the design of next‐generation green environmental functional materials.

Liu and co‐workers designed and prepared an ultrathin two‐dimensional metal–organic framework (MOF) nanosheet loaded with abundant SO₄ ^{2 −} active sites on its surface for the efficient and selective removal of Hg^{2 +} from water [161]. The material achieved an adsorption capacity of 989.19 mg/g for Hg^{2 +}, with removal efficiencies exceeding 94 % in real water samples (acidic groundwater, battery wastewater, and petrochemical wastewater), and exhibited excellent selectivity and anti‐interference capability (Figure 18a). This research delivers a new material approach that combines high efficiency with practical applicability, aiming at the remediation of heavy metal‐contaminated water. Zhang and co‐workers used chloride anions as coordination centers and constructed an anion‐coordination‐based supramolecular organic framework (chloride‐SOF) with a flexible oligopyrrole ligand [162]. The material forms a crystalline structure through multiple intermolecular interactions and A‐B‐C‐type stacking of 2D honeycomb layers, exhibiting good thermal stability and retaining its framework integrity after desolvation. The desolvated chloride‐SOF was applied to treat contaminated water containing 100 mg/L picric acid (PA), reducing the PA concentration to the low ng/L (ppt) level (Figure 18b). Mechanistic studies indicate that PA capture is achieved mainly through anion exchange and adaptive structural transformation, rather than conventional pore‐size selectivity. This work demonstrates the potential of anion‐coordination‐based SOFs as structurally transformable materials for hazardous waste removal. These findings demonstrate that through rational design of coordination centers (metal ions or anions) and organic ligands, self‐assembled materials with high selectivity, high capacity, and structural adaptability can be constructed, which provides new insights for the development of smart and reconfigurable environmental remediation materials.

FIGURE 18.

(a) Adsorption capacity and removal efficiency of the SO₄ ²⁻‐loaded ultrathin 2D MOF nanosheet for Hg²⁺ in various real water samples. Reproduced with permission [Ref 161]. Copyright at 2025 Elsevier B.V. (b) Schematic illustration of the adaptive structural transformation and anion‐exchange mechanism of chloride‐SOF for picric acid (PA) capture. Reproduced with permission [Ref 162]. Copyright at 2025 American Chemical Society.

5. Computational and Theoretical Approaches of Dynamic/Adaptive Self‐Assembly Systems

Beyond their use in experimental settings, computational and theoretical methods have become essential tools for understanding and predicting how dynamic and adaptive self‐assembled systems behave. Three key approaches, such as molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and machine learning (ML) techniques, each provide distinct perspectives on the mechanisms, energy landscapes, and rational design of self‐assembling materials [163, 164, 165]. ​

MD simulations allow researchers to observe the dynamic evolution of supramolecular architectures at either the atomistic or coarse‐grained level. For example, Bochicchio and colleagues used coarse‐grained MD to uncover the inherent complexity of supramolecular polymer systems. Their work showed that these systems are made up of highly dynamic molecular components that constantly exchange and reshape the assemblies, findings that challenge the traditional static understanding of such materials (Figure 19a) [166]. In related research, the same team combined atomistic and coarse‐grained MD simulations to characterize monomer exchange mechanisms at the submolecular level. They demonstrated that exchange arises from structural defects within fibers, linking defect dynamics to the materials’ ability to self‐heal and reconfigure (Figure 19b) [167]. ​

FIGURE 19.

(a) Minimalistic self‐assembly model caption: M monomers directionally self‐assemble via central red beads (gray beads ensure directionality); coarse‐grained simulations show that increasing the central‐bead interaction strength from 40 to 50 kJ/mol transforms randomly distributed monomers into ordered fibers. Reproduced with permission [Ref 166]. Copyright at 2022 Springer Nature. (b) Mechanism of monomer exchange in BTA‐C6 fibres in the gas phase or in organic solvent. Reproduced with permission [Ref 167]. Copyright at 2017 Springer Nature.

DFT calculations offer a robust way to map the energy landscapes of supramolecular systems, connecting thermodynamic stability to observable functions. Tantakitti and co‐workers used DFT to study two typical systems: peptide amphiphiles assembled through hydrogen‐bonded β‐sheets and chromophore amphiphiles driven by π‐orbital overlaps [168]. They found that the lowest energy points (minima) in supramolecular energy landscapes are determined by a balance between competing attractive forces and electrostatic repulsion (Figure 20a). The order in which these interactions come into play dictates whether the final product settles in a thermodynamically stable state or a metastable minimum. Importantly, the researchers established a direct link between the topology of the energy landscape and biological function: the thermodynamically favored product promotes cell adhesion, while the metastable product interferes with it. In parallel, machine learning has recently opened up new possibilities for analyzing and predicting self‐assembly behaviors. Brown and colleagues developed a data‐driven strategy that uses unsupervised ML clustering of Smooth Overlap of Atomic Position data from equilibrium MD simulations to classify soft supramolecular assemblies [169]. Their approach acts as a “defectometer,” enabling comparisons between different supramolecular materials based on the structural dynamics of their ordered and disordered local molecular environments (Figure 20b).

FIGURE 20.

(a) Schematic representation of the energy landscape. Reproduced with permission [Ref 168]. Copyright at 2016 Springer Nature. (b) Classification of supramolecular polymers based on the structural/dynamical features of their molecular motifs. Reproduced with permission [Ref 169]. Copyright at 2022 Springer Nature.

Taken together, these computational and theoretical methods not only shed light on the hidden dynamic principles that govern supramolecular assembly but also provide predictive capabilities to accelerate the rational design of next‐generation adaptive materials. In doing so, they bridge the gap between molecular design, emergent structure, and macroscopic function.​

6. Conclusion and Outlook

Dynamic self‐assembly systems are a prominent research frontier in smart materials. They enable materials to perceive external changes and respond intelligently, a transitioning from static assembly to dynamic adaptation. This endows them with flexibility and controllability. Among various material classes, supramolecular hydrogels, DNA‐based nanostructures, and peptide‐amphiphile systems are most promising due to their biocompatibility, tunable responsiveness, and ease of functionalization. Host‐guest systems (e.g., cyclodextrin/adamantane) and dynamic covalent chemistries (e.g., disulfide and boronate ester bonds) shoe strong potential for constructing reversible, multi‐stimuli‐responsive platforms. Nevertheless, translation into practice faces challenges. Key technical barriers include: (i) the trade‐off between rapid responsiveness and mechanical robustness, which hinders device integration, and (ii) the lack of standardized characterization and performance evaluation protocols. Additionally, achieving balance among stability, responsiveness, and biocompatibility remains difficult, limiting clinical applicability.

To provide practical guidance, we briefly overview key characterization techniques. Optical microscopy (confocal, super‐resolution) enables real‐time visualization but is diffraction‐limited and often requires labeling. Electron microscopy (SEM, TEM, cryo‐EM) offers nanometer detail, though sample preparation may perturb out‐of‐equilibrium states [170]. Atomic force microscopy (AFM) probes mechanical and hydration in near‐native conditions, but tip interactions can induce artifacts. Scattering techniques are indispensable: dynamic light scattering (DLS) reports size distributions and kinetics, while small‐angle X‐ray and neutron scattering (SAXS/SANS) provide time‐resolved hierarchical insights [171]. However, interpreting data from polydisperse or rapidly evolving systems requires careful modeling. Spectroscopic methods (e.g., fluorescence, circular dichroism, NMR) track molecular‐level conformational changes and binding events [172]. No single technique captures full complexity; multi‐method correlative approaches are essential, especially for non‐equilibrium systems.

To critically evaluate the field, we compare five regulation types: light, temperature, pH, guest molecules, and metal‐ligand coordination. Light offers high resolution but poor tissue penetration and photodamage. Temperature is reversible yet lacks precision and can harm living systems via bulk heating. pH exploits physiological gradients but has narrow ranges and buffer interference. Guest‐molecule regulation enables selective assembly but often requires competitive guests. Metal‐ligand coordination provides tunable binding but raises toxicity and stability concerns. Multi‐responsive systems offer synergistic control at increased complexity. Formulation limitations also hinder translation: stability suffers from drift, hydrolysis, or aggregation; scalability is limited by low yields and poor reproducibility; biocompatibility includes immunogenicity and off‐target effects. For injectable formulations, rheology must prevent clogging or premature release. Addressing these issues is essential for real‐world applications.

Beyond these challenges, several emerging frontiers are reshaping the field. Dissipative or out‐of‐equilibrium assembly moves toward fuel‐driven transient systems (e.g., ATP‐fueled assemblies). precise regulation of assembly‐disassembly kinetics and biocompatible fuel cycles remain hurdles [173, 174, 175]. Multicomponent cooperative assembly integrates orthogonal building blocks for cascade responses and adaptive behavior, but controlling selectivity without cross‐interference is a challenge [176, 177, 178]. Integration with synthetic biology enables artificial organelles, signaling networks, and living material interfaces, yet interfacing synthetic materials with living systems at the molecular level is difficult [179, 180, 181, 182]. Systems chemistry and emergent behavior show that local interactions can give rise to global behaviors(e. g., self‐replication, pattern formation). Harnessing this for material design is a paradigm shift, but predicting emergent behaviors from molecular rules remains nascent [183, 184, 185].

Addressing these challenges requires collaboration and continuous innovation. The future will focus on the rational design of intelligent building blocks that integrate stability, rapid responsiveness, and biocompatibility. This will transition materials from single to multi‐signal integration (light, temperature, pH, and enzymes), producing coordinated responses akin to biological systems. The field must embrace non‐equilibrium, multi‐component, and systems‐level approaches to bridge synthetic materials and life‐like functionalities. Efforts will expand applications in targeted drug delivery, adaptive electronics, and environmental remediation. Ultimately, we aim to construct life‐like material systems with real‐time perception, precise decision‐making, and active execution capabilities, providing next‐generation material support for healthcare, energy, and the environment.

Funding

This research was supported by the Science and Technology Research Project of the Education Department of Jilin Province, grant number JJKH20261157KJ.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.