Polymerization‐Induced Self‐Assembly of Nonlinear Polymers

ABSTRACT

Polymerization‐induced self‐assembly (PISA) has become a scalable route to block copolymer nanoparticles with tunable morphologies, but most established PISA formulations focus on linear architectures. This review surveys recent progress in extending PISA to nonlinear polymers—highlighting how polymer topology reshapes nucleation, packing, interfacial curvature, and ultimately nanoparticle morphology—while also positioning PISA as a practical method for synthesizing architecturally complex macromolecules. Key advances are summarized across star, graft, bottlebrush, branched, and cyclic polymers. Finally, we also discuss future opportunities of PISA of nonlinear polymers that may provide some inspirations for researcher in this area.

This review summarizes the latest research advances in the PISA of nonlinear polymers, focusing on typical nonlinear polymer systems including star, graft, bottlebrush, branched, and cyclic polymers. It systematically elaborates on the core idea of achieving the controlled synthesis of nonlinear block copolymer nanoparticles through precise topological structure design, details the mainstream synthetic strategies and technical methods for preparing nonlinear polymer nanoparticles currently, and presents an outlook on the existing limitations, potential challenges, and future development directions in this field.

1. Introduction

Polymer nanoparticles with precisely tunable size and morphology have become an important class of soft nanomaterials for applications in drug delivery, catalysis, bioimaging, Pickering emulsions, photonics, hydrogels, and functional coatings, among others [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. In laboratories, a variety of self‐assembly strategies—including solution self‐assembly (SSA) [17, 18, 19, 20], evaporation‐induced self‐assembly (EISA) [21, 22, 23, 24, 25], layer‐by‐layer assembly [26, 27, 28], and crystallization‐driven self‐assembly (CDSA) [29, 30, 31, 32]—are routinely used to access diverse nano‐objects such as spheres, worms, nanofibers, vesicles, and more complex morphologies (e.g., doughnut‐ and jellyfish‐like structures). However, these approaches share several common limitations: they typically rely on the prior synthesis of well‐defined amphiphilic block copolymers and involve multi‐step, processing‐intensive protocols. Moreover, the solids content is relatively low (typically < 1% w/w). Together, these requirements complicate scale‐up and hinder broader translation of block copolymer nanoparticles toward practical applications.

Over the past decade, polymerization‐induced self‐assembly (PISA) has emerged as a powerful platform for scalable synthesis of block copolymer nanoparticles with diverse morphologies [33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67]. Typically, a soluble homopolymer is first synthesized and then chain‐extended with a second monomer in a selective solvent. As the second block reaches a critical degree of polymerization (DP), in situ self‐assembly is triggered, yielding diblock copolymer nano‐objects. Remarkably, the solids content can be up to 50% w/w, allowing the scalable production of block copolymer nano‐objects. By varying block compositions and reaction parameters (e.g., solvent, reaction temperature, pH, initiator/chain transfer agent chemistry, and solids content), a wide range of morphologies‐including spheres, worms, vesicles, microspheres, and large‐compound vesicles‐can be prepared at high solids contents. These nanoparticles have shown potential in drug delivery, catalysis, photonic crystals, nanoreactors, lubricant, Pickering emulsion, toughening agents, and beyond [68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79].

While substantial progress has been achieved in PISA, most formulations have emphasized producing well‐defined linear block copolymers. Over the past few years, numerous review articles on PISA have been published by a range of research groups [34, 35, 41, 45, 46, 47, 49, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99]; however, none have focused specifically on PISA of nonlinear polymers (e.g., branched, graft copolymer, bottlebrush polymer, and other topologically complex architectures). Polymer architecture is a key factor governing self‐assembly in both bulk and solution [17, 100, 101, 102]. Importantly, PISA is not only a convenient route to polymer nanoparticles but also a heterogeneous polymerization technique that enables efficient synthesis of well‐defined macromolecules. In this review, we summarize key advances in the PISA of nonlinear polymers and discuss emerging opportunities and challenges. Cases related to the PISA of various nonlinear topological polymers have been summarized in Table 1 and will be discussed in detail in the subsequent chapters.

TABLE 1.

Summary of polymers, solvents, particle morphologies, polymerization methods, and references for PISA of nonlinear polymers.

Polymer architecture	Polymers	Solvent	Particle morphologies a	Polymerization technique	Ref.
Star Polymer	core cross‐linked star (CCS) polymers	Water	S, W	RAFT	[103, 104, 105]
	μ‐A(BC)C miktoarm star polymer	Water	S, W, V	RAFT	[106]
	PEG‐(PDAAMn)2	Water	S, V	RAFT	[107]
	(mPEG)3‐PS	Methanol/Water	S, W, V	RAFT	[108]
	TPE‐(POEGA)n‐(PBzMA)4−n	Methanol/Water	S, W, V	RAFT	[109]
	[P4VP‐b‐PS]n	Methanol/Water	S, V, porous spheres	RAFT	[110]
	[PDMAx‐b‐PDAAMy]n	Water	S, W, V	RAFT	[111]
	(PDMAx‐PSty‐TTC‐Z)4	Methanol/Water	S, W, V	RAFT	[112]
	(PDMAx‐PDAAMy)3	Water	S, W, V	RAFT	[113]
	POSS‐(PNIPAM‐b‐PS)8	Ethanol/Water	S, V	RAFT	[114]
	PPI‐(PLP‐b‐PZLL)8	Acetonitrile /Water	S, W, V	ROP	[115]
	star s‐PNIPAM‐b‐PS	Ethanol/Water	S	RAFT	[116]
	μ‐ABC PDMA‐PBMA‐PS	Ethanol/Water	Multicompartment Nanoparticles	CuAAC, ATRP and RAFT	[117]
	μ‐ABC mPEG113‐PHPMA‐PtBA	Water	S, W, V	RAFT	[118]
Graft copolymer	glycosylated graft copolymer	Water	S, W, V	RAFT	[119, 120, 121, 122, 123, 124]
	PLMA‐g‐PBzMA graft copolymer	n‐dodecane	S, W, V, LCVs	RAFT	[125]
	PVA‐g‐PHPMA& PVA‐g‐PDAAM	Water or NaCl solution	S	RAFT	[126]
	PPEGMA‐co‐[PBTPEMA‐g‐PS]	Methanol/Water	S, V	ATRP/RAFT	[127]
	alginate‐g‐PMMA	Methanol/Water	S	SET‐LRP	[128]
Bottlebrush polymer	PNB‐g(PEG‐branch‐PS/PBzMA)	Methanol/Water	S, V	ROMP/RAFT	[129]
	P(NB‐g‐PEG45)m‐b‐P(NB‐g‐PS)n	Methanol	S, disk‐like micelles	ROMP/PISA	[130]
	PPEGMA‐co‐P(CEPMA‐g‐PHPMA‐b‐PGlyMA)	Water	S, W, V	RAFT	[131]
	P[PEGMA‐co‐(HEMA‐g‐PS)]	Ethanol/Water	S	RAFT	[132]
Branched polymer	mPEG113−CEPA/CEPA−HEMA)−PHPMA	Water	S, W, V	RAFT	[133]
	PHPMA‐co‐P(mPEG113‐CTM)	Water	S, W, V	RAFT	[134]
	(BTPA‐HEA)‐PS‐PDMA	Methanol/Water	S, W, V	RAFT	[135]
	PEG112‐P(AB2‐Bn)	Methanol/Water	S, LCVs	CuAAC	[136]
Cyclic polymer	CPEO‐b‐PBzMA & CPEO‐b‐ PPFSt	Ethanol/Water or Ethanol/ N,N‐dimethylformamide	S, W, V	RAFT	[137]

^a S: Spheres, W: Worms, and V: Vesicles, LCVs: Large compound vesicles.

2. Star Polymers

Star polymers are well‐defined branched macromolecules in which multiple polymer arms are covalently connected to a single junction point or core, giving rise to a star‐like structure. This distinctive topology endows star polymers with self‐assembly characteristics, solution behavior, and rheological properties that differ from those of analogous linear polymers [138]. Star polymers are typically synthesized using either an “arm‐first” strategy or a “core‐first” strategy, and both have also been utilized in PISA for the synthesis of star polymer nanoparticles.

An's group [103, 104, 105] reported the efficient synthesis of core cross‐linked star (CCS) polymers by reversible addition‐fragmentation chain transfer (RAFT)‐mediated PISA using linear macromolecular chain transfer agents (macro‐CTAs) in the presence of divinyl cross‐linkers. They showed that introducing an appropriate number of spacing monomers could promote the formation of CCS polymers due to the amphiphilicity of the polymer chains. The functionality and composition of these CCS polymers could be tuned by varying the macro‐RAFT agent structure, and the CCS polymers could serve as efficient emulsifiers for oil‐in‐water emulsion. Very recently, our group [106] performed green light‐activated photoiniferter polymerization of glycerol methacrylate using an ω, ω‐heterodifunctional macro‐RAFT agent and related diblock copolymer macro‐RAFT agents featuring one RAFT group located between two blocks and another at the chain end. Using these macro‐RAFT agents under PISA conditions, μ‐A(BC)C miktoarm star polymer nanoparticles were obtained. Compared to an ABC triblock copolymer, the μ‐A(BC)C architecture favored nanoparticle fusion and thus promoted higher‐order morphologies.

Star‐like multifunctional macro‐CTAs provides an attractive route to star block copolymer nanoparticles by PISA. An, Sumerlin, and coworkers [107] synthesized an ω, ω‐difunctional macro‐RAFT agent and used it to mediate aqueous RAFT dispersion polymerization of diacetone acrylamide (DAAM), yielding AB₂ star polymers. The star polymer architecture favored higher‐order morphologies relative to a linear analogue. Zhang et al. [108] prepared macro‐CTAs with three methoxy poly(ethylene glycol) (mPEG) arms and used them in RAFT dispersion polymerization of styrene (St) to generate (mPEG)₃‐PSt star polymer nanoparticles. A direct comparison between (mPEG₇₅₀)₃‐PSt and linear mPEG₂₀₀₀‐b‐PSt showed that the A₃B star architecture favored the formation of larger vesicles. More recently, the same group [109] synthesized aggregation‐induced emission (AIE)‐activated miktoarm star polymer nanoparticles by RAFT dispersion polymerization of benzyl methacrylate (BzMA) using AIE‐activated macro‐RAFT agents, demonstrating that arm number can control both nanoparticle morphology and photoluminescence characteristics.

Zhang's group [110] further reported the synthesis of star block copolymer nanoparticles via RAFT dispersion polymerization using an R‐type star‐like macro‐RAFT agent, showing that nanoparticle size and morphology correlate strongly with arm number and that star architecture can favor higher‐order morphologies compared with linear counterparts. Wang et al. [111] prepared R‐type star‐like macro‐RAFT agents with different arm numbers and used them in aqueous RAFT dispersion polymerization of DAAM. At high arm numbers, aggregation occurred due to an increased possibility of interparticle bridging. This issue was mitigated by using a binary mixture of a star‐like macro‐RAFT agent and a monofunctional macro‐RAFT agent, enabling colloidally stable nanoparticles with various morphologies. Because R‐type macro‐RAFT agents often place solvophobic segments at the periphery, particle bridging can be exacerbated during PISA, making it challenging to access high‐arm‐number star polymers and well‐defined morphologies. Our group [112] reported star block copolymer nanoparticles via RAFT dispersion polymerization of St using Z‐type and R‐type star‐like macro‐RAFT agents. The arm sequence was controlled such that the solvophilic block was peripheral in the Z‐type case, whereas the solvophobic block was peripheral in the R‐type case, highlighting the critical role of architecture in RAFT‐mediated PISA (Figure 1). TEM and size exclusion chromatography (SEC) analysis confirmed that the Z‐RAFT approach is better suited for preparing star block copolymer nanoparticles without compromising the control over the molecular weight and morphology. Mellot et al. [113] similarly synthesized 3‐arm star block copolymer nanoparticles via aqueous RAFT dispersion polymerization of DAAM using a Z‐type trifunctional macro‐RAFT agent. Zhang's group [114] also used Z‐RAFT‐PISA to synthesize well‐defined 8‐arm star block copolymers nanoparticles with a polyhedral oligomeric silsesquioxanes (POSS) core; the resulting POSS‐based vesicles can be used as thermal insulation materials. Tinajero‐Díaz et al. [115] performed ring‐opening dispersion polymerization of benzyl‐L‐glutamic acid N‐carboxyanhydride (BLC‐NCA) using ε‐poly(lysine) (εPL) as the reactive surfactant, forming amphiphilic star‐like copolypeptides (εPL backbone, PBLG side chains) that self‐assembled into colloidally stable nanoparticles.

FIGURE 1.

Schematic illustration of RAFT‐Mediated PISA of St using R‐type and Z‐type tetrafunctional Macro‐RAFT Agents [112]. Copyright 2020, American Chemical Society.

Seeded polymerization using PISA‐derived nanoparticles offers another route to star polymer nanoparticles. Zhang's group [116] synthesized linear block copolymers nanoparticles via RAFT‐PISA, then added divinyl cross‐linkers to form CCS nanoparticles. Using this method, star polymers with arm numbers up to ∼300 were achieved and visualized by TEM and displayed interfacial properties distinct from linear analogs. The same group [117] also reported μ‐ABC miktoarm star polymer nanoparticles prepared by copper(I)‐catalyzed click reaction followed by seeded RAFT dispersion polymerization, with size and morphology controlled by arm length; these μ‐ABC miktoarm star polymer nanoparticles significantly reduced the interfacial tension in n‐hexane/water. Very recently, our group [118] introduced orthogonal RAFT polymerization into PISA using an ω,ω‐heterodifunctional macro‐RAFT agent, generating block copolymer nanoparticles bearing unreacted RAFT groups at the interface. These nanoparticles could be used as seeds for seeded RAFT dispersion polymerization to yield μ‐A(BC)C miktoarm star block copolymer nanoparticles, with morphology readily tuned by DP. Notably, the miktoarm architecture enhanced the morphological stability of worm‐like micelles during seeded RAFT dispersion polymerization (Figure 2).

FIGURE 2.

Photoinitiated seeded RAFT polymerization of tert‐butyl acrylate using mPEG₁₁₃‐PHPMA₂₂₀‐BTC worms as seeds and TEM imagines of the obtained μ‐A(BC)C miktoarm star block copolymer nanoparticles with variety targeted DP of PtBA [118]. Copyright 2022, American Chemical Society.

3. Graft Copolymers

Graft copolymers are nonlinear polymers in which multiple polymeric side chains are covalently attached to a polymer backbone. They are widely used as compatibilizers, surface modifiers, lubricant, and functional materials, as their architecture enables the independent tuning of backbone and side‐chain properties [139, 140, 141, 142, 143, 144, 145]. Graft polymers have also attracted considerable interest in self‐assembly [146, 147, 148]. Here, we summarize recent studies applying graft copolymers in PISA.

Ferji's group [119, 120, 121, 122, 123, 124] developed a PISA platform for to prepare glycosylated graft copolymer nanoparticles by grafting multiple RAFT agents onto a linear polysaccharide backbone. The resulting macro‐RAFT agent regulated photoinitiated RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA) in water, yielding colloidally stable graft copolymer nanoparticles. Systematic studies showed that increasing grafting density and side‐chain length promoted evolution toward higher‐order morphologies. PISA was essential for obtaining higher‐order Dex‐g‐PHPMA_n assemblies: nanoprecipitation yielded only spheres, while emulsion‐solvent evaporation and film rehydration led to macroscopic precipitation. An unusual intermediate morphology (multicompartment vesicles) was also observed, which could fuse into large compound nanoparticles [149].

Perrier's group [125] reported PISA of poly(lauryl methacrylate)‐graft‐poly(benzyl methacrylate) (PLMA‐g‐PBzMA) copolymers in a non‐polar solvent using PLMA as the graft copolymer backbone, while PBzMA side chains become gradually solvophobic during the polymerization. Specifically, poly(lauryl methacrylate‐co‐hydroxyethyl methacylate) (P(LMA‐co‐HEMA)) copolymers were first synthesized by RAFT polymerization, then esterified with a carboxyl‐functionalized RAFT agent to introduce pendant RAFT groups. Subsequent RAFT dispersion polymerization of BzMA in n‐dodecane generated PLMA‐g‐PBzMA graft copolymer nanoparticles, with morphology evolving from spheres to worms, vesicles, and larger‐compound vesicles as the PBzMA volume fraction increased. Gibson's group [126] attached RAFT agents onto commercially available poly(vinyl alcohol) (PVA) to produce a water‐soluble PVA‐based macro‐RAFT agent, which enabled aqueous RAFT‐mediated dispersion polymerization of DAAM to form grafted block copolymers and spherical nanoparticles (200‐400 nm) showing ice growth‐modulating behavior.

Precisely controlling the number and distribution of pendant RAFT groups on a backbone remains challenging when relying on esterification of hydroxy‐functional polymers with carboxyl‐functional RAFT agents. To address this limitation, our group [127, 150] employed orthogonal RAFT polymerization and orthogonal RAFT‐atom transfer polymerization (ATRP) to synthesize multifunctional macro‐RAFT agents with tunable pendant RAFT number and distribution. These macro‐RAFT agents mediated RAFT dispersion polymerization of St to generate a variety of graft copolymer nanoparticles, revealing that both side chain number and distribution significantly influenced the self‐assembly and final morphology under PISA conditions (Figure 3).

FIGURE 3.

Schematic illustration of macro‐RAFT agents with different RAFT group distribution and TEM images of resultant graft copolymer assemblies [127]. Copyright 2024, American Chemical Society.

Beyond RAFT polymerization, other polymerization techniques have also been integrated into PISA for graft copolymer nanoparticles. Kapishon et al. [128] used single electron transfer living radical polymerization (SET‐LRP) in a PISA process of methyl methacrylate (MMA) to produce alginate‐based amphiphilic graft copolymer micelles with diameters ranging from 50 to 300 nm.

4. Bottlebrush Polymers

Bottlebrush polymers are a prominent subclass of graft polymers characterized by densely grafted side chains and highly extended conformations. Dense grafting rigidifies the backbone, producing physical, rheological, and self‐assembly behaviors distinct from linear or star architectures [151]. Bottlebrush polymers have been explored as templates, elastomers, organic optoelectronic materials, antifouling coatings, and surfactants [85, 152, 153, 154, 155, 156, 157]. In self‐assembly, bottlebrush block copolymers often form larger microphase‐separated domains than linear analogues, facilitating aggregation and ordered assemblies. The broad design space—grafting density, backbone length, and side‐chain length—enables fine structural control.

Hou et al. [129] used ring‐opening metathesis polymerization (ROMP) of polynorbornene‐g‐(poly(ethylene glycols)‐RAFT agent) to synthesize multifunctional macro‐RAFT agents, which then mediated RAFT dispersion polymerization of St to produce Janus bottlebrush polymers. Inter‐ and intramolecular cross‐linking was negligible under the polymerization conditions, enabling high‐yield synthesis. Using a related approach, they also prepared bottlebrush block copolymer nanoparticles and observed a morphological transition from spheres to disk‐like micelles during PISA, attributed to the rigidity of PS segments as shown in Figure 4. [130]

FIGURE 4.

Scheme illustrations for (a) the structure of the bottlebrush macro‐RAFT agent; (b) RAFT dispersion polymerization and in suit assembly for the synthesis of bottlebrush block copolymer nanoparticles [130]. Copyright 2023, American Chemical Society.

Liu et al. [131] reported the synthesis of bottlebrush block copolymer nanoparticles via aqueous photoinitiated RAFT dispersion polymerization of HPMA using poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA)‐based multifunctional macro‐RAFT agents. Compared with bottlebrush‐linear BCP assemblies sharing the same solvophilic block, the bottlebrush block copolymers favored higher‐order morphologies at similar target DPs and monomer concentrations, consistent with architectural constraints reducing interfacial curvature as shown in Figure 5. Mei et al. [132] synthesized P(PEGMA‐co‐HEMA) with high HEMA content, converted it into a multifunctional macro‐RAFT agent via reaction with a carboxyl‐functional RAFT agent, and used it to mediate RAFT dispersion polymerization of St to form Janus bottlebrush polymer nanoparticles; nanoparticle size depended on backbone length and the solvophilic/solvophobic ratio.

FIGURE 5.

Schematic illustration for RAFT‐PISA of bottlebrush‐linear block copolymers (left) and bottlebrush block copolymers (right) [131]. Copyright 2022, Wiley‐VCH.

5. Branched Polymers

Branched polymers contain branching points within the backbone, producing 3D architectures beyond linear chains. Depending on branching density and regularity, they are categorized as conventional branched, hyperbranched, or dendritic polymers [158, 159]. Self‐condensing vinyl polymerization (SCVP) is an attractive route to branched polymers, typically via copolymerization of vinyl monomers with inimer units or chain transfer monomers (CTMs); the degree of branching is tunable by feed composition [160, 161, 162, 163, 164, 165, 166, 167, 168, 169].

Despite broad applications of branched polymers in compatibilization, coatings, catalysis, and drug delivery [170, 171, 172, 173, 174, 175, 176, 177, 178], their use in PISA remains comparatively underexplored. Liu and coworkers [133] reported the first PISA of branched block copolymers via aqueous RAFT dispersion SCVP of HPMA in the presence of a CTM. Increasing the CTM content increased the degree of branching and the packing parameter, promoting access to higher‐order morphologies. A disulfide‐lined CTM enabled reduction‐responsive branched block copolymer nanoparticles: treating with 1,4‐dithiothreitol converted worm‐like micelles to spherical micelles, consistent with a reduced packing parameter following disulfide cleavage. Very recently, Lin et al., [134]. synthesized an ω,ω‐macro‐CTM via selective esterification and used it to mediate RAFT dispersion polymerization of HPMA, showing that the heterogeneous environment promoted SCVP by decreasing interchain distance; amphiphilic branched block copolymers were obtained in one‐step, with the degree of branching tunable via CTM addition.

Using branched macro‐RAFT agents in PISA is another direct approach, but RAFT group placement strongly influences PISA outcomes. Cai et al. [135] synthesized Z‐type and R‐type branched macro‐RAFT agents via RAFT‐SCVP and compared their performance in RAFT‐PISA (Figure 6). The R‐type branched macro‐RAFT agent caused precipitation, attributed to solvophobic growth at the periphery enhancing interparticle bridging, whereas the Z‐type branched macro‐RAFT agent favored internal solvophobic growth and yielded colloidally stable branched block copolymer nanoparticles with well‐defined morphologies. Other branched macro‐RAFT agents with interior RAFT placement have similarly enabled stable branched nanoparticles under PISA conditions [179, 180, 181].

FIGURE 6.

Schematic illustration for RAFT‐PISA of branched block copolymers using a R‐type branched macro‐RAFT agent (a) or Z‐type branched macro‐RAFT agent (b). [135] Copyright 2022, American Chemical Society.

Because radical polymerization is stochastic, SCVP typically yields statistically distributed branched structures lacking strict symmetry. Yuan, Gao and, coworkers [136] reported a click‐based strategy to form linear–dendritic nanoparticles using an AB₂‐type monomer: triazole–amine‐functionalized mPEG served as a macro‐initiator, and a benzyl derivative bearing one alkyne and two azides served as the monomer. Copper‐catalyzed azide–alkyne cycloaddition dispersion polymerization in methanol/water produced colloidally stable linear–dendritic nanoparticles, although only spherical morphologies were obtained and initiation efficiency was relatively low.

6. Cyclic Polymer

Cyclic polymers are closed‐loop macromolecules formed by end‐to‐end joining of polymer chains, eliminating chain ends. Relative to linear analogues, cyclic polymers exhibit distinct conformations and properties, including reduced hydrodynamic volume, elevated glass‐transition temperatures, and lower melt viscosities, motivating applications in surface functionalization and drug delivery [182, 183, 184, 185, 186, 187, 188, 189, 190, 191]. Considerable effort has also been devoted to cyclic block copolymer self‐assembly, revealing rich morphology and dynamics [192, 193, 194, 195, 196, 197, 198, 199].

To the best of our knowledge, only one study has reported PISA of cyclic polymers. Hong and coworkers [137] reported the first PISA using a cyclic macro‐RAFT agent synthesized via intramolecular cyclization of a bifunctional anthracene‐PEO as shown in Figure 7. While cyclic and linear macro‐RAFT agents exhibited broadly comparable RAFT dispersion kinetics and similar overall morphology trends across core‐forming monomers, the cyclic system showed a prolonged nucleation period and a stronger tendency toward lower‐order morphologies under otherwise identical conditions. For example, at a target DP of 150, linear block copolymers formed mixed spheres and worms, whereas cyclic block copolymers formed only spheres. This was attributed to the higher effective solubility of the solvophilic block in the cyclic block copolymers, which reduces the driving force for microphase separation and thereby suppresses access to higher‐order morphologies.

FIGURE 7.

Schematic illustration for the synthesis of diblock copolymer nano‐objects via polymerization‐induced self‐assembly (PISA) using (a) cyclic and (b) linear macro‐RAFT agents, respectively [137]. Copyright 2022, Editorial Office of JUSTCW.

7. Conclusions and Future Opportunities

Over the past 15 years or so, PISA has become a powerful technique for the scalable synthesis of linear block copolymer nanoparticle with diverse morphologies. Extensive efforts have tuned morphology by changing block composition and reaction parameters. Polymer architecture is well‐known to modulate self‐assembly, yet PISA of nonlinear polymers remains comparatively underdeveloped. This review summarized advances in PISA of star, graft, bottlebrush, branched, and cyclic polymers, highlighting that architecture strongly affects PISA pathways and final morphologies while also underscoring PISA as an efficient technique to architecturally complex macromolecules. Nevertheless, key challenges remain and new opportunities are emerging.

Most current PISA formulations for nonlinear polymers rely on RAFT polymerization. This is mainly because RAFT polymerization has milder reaction conditions compared with other polymerization methods and a wider range of monomer selectivity. In addition, within the framework of nonlinear polymers, the Z/R structure of RAFT agents can more flexibly meet the requirements of structural design. However, RAFT end groups may impart odor and yellow coloration and often require removal for practical applications [200]. Expanding nonlinear‐polymer PISA to other polymerization chemistries (e.g., nitroxide‐mediated polymerization [201] and ring‐opening polymerization [202]) is therefore desirable. Structural control also remains limited: arm numbers in star polymers are typically constrained to preserve colloidal stability; graft/bottlebrush backbones are often limited in length; branching degrees in PISA‐derived branched polymers are usually low, and accessing truly hyperbranched structures remains challenging. Scalable synthesis of cyclic macro‐RAFT agents also remains difficult. Advances in polymer synthesis may provide new opportunities to refine architectures under PISA conditions [163, 203].

Finally, nonlinear architectures offer unique opportunities to incorporate functional linkages or groups that impart stimuli responsiveness, degradability, and other advanced properties. However, most studies to date have emphasized synthesis and morphology control rather than application‐driven design. Developing functional nonlinear polymer nanoparticles tailored to specific applications represents a promising direction.

Conflicts of Interest

The authors declare no conflicts of interest.

Biographies

Ruiming Wang received his Bachelor's degree in Polymer material and Engineering in Guangdong University of Technology in 2021 and complicated his master's studies under the supervision of Prof. Jianbo Tan in 2024 at Guangdong University of Technology. He is currently pursuing a doctoral degree at Guangdong University of Technology. His research focuses on the synthesis of functional polymer materials.

Li Zhang graduated from Sun Yat‐Sen University in 1994. After a two‐year postdoc stint at South China University of Technology (1994–1996), she accepted a faculty position at South China Normal University. She was promoted to professor in 2000 and moved to Guangdong University of Technology in 2008. Her current research interests cover photoinitiated polymerization, functional polymeric particles, and reversible deactivation radical polymerization (RDRP).

Jianbo Tan received his B.S. (2009) and Ph.D. (2014) degrees from Sun Yat‐Sen University under the supervision of Prof. Zhaohua Zeng. He joined Prof. Mitchell A. Winnik's group (University of Toronto, 2012–2014) as a visiting Ph.D. student. After graduation, he accepted a faculty position at Guangdong University of Technology in 2015 and promoted to professor in 2019. His current research interests cover RDRP, photoinitiated polymerization, polymerization‐induced self‐assembly, functional polymeric particles for various applications, and inorganic/organic nanocomposites.