Table 1.
Various advanced prototypes of MSNs conveying therapeutic cargo for various stimuli-responsive delivery
| Type of Stimuli | Advanced composites | Advancement/modifications | Morphology | Cargo | Particle size | Targeted site/outcome | Refs |
|---|---|---|---|---|---|---|---|
| pH-responsive | V7-RUBY | Wormhole pore, Chitosan-coated, and V7 peptide-modified | Spherical | IR780 dye, paclitaxel, or carboplatin | < 40 nm | The tumor-specific-targeted release presented improved therapeutic effects against the orthotopic ovarian tumors | [258] |
| LB-MSN-OVA | Lipid bilayer-coated over the surface | Rectangular | Ovalbumin | ~ 200 nm | MSNs-encapsulated in microneedle arrays showed exceptional intradermal antigen delivery | [260] | |
| CS-PtNPs@Zn-MSNs | CS-coated over the MSNs | Spherical | DOX | ~ 100 nm | pH-responsive CS degradation facilitated the convenient delivery of MSNs intracellularly, overcame the MDR, and offered PtNPs-assisted deep tumor penetration | [110] | |
| Triple-labeled MSNs | YQRLGC-peptide conjugated, PEI/PEG/THPMP | Spherical | FITC, OG, and RITC | ~ 200 nm | These lysosome-targeted nanoprobes enriched the understanding of the fate of MSNs intracellularly | [257] | |
| FCA@mSiO2 | Fe3O4 coated carbon/silver (FCA) as core and mesoporous silica as shell | Core–shell | Fe2+, artemisinin | ~ 200 nm | Artemisinin-loaded FCA@mSiO2 presented the acid-specific release of Fe2+ ions to non-enzymatically convert artemisinin to toxic species for cancer ablation | [430] | |
| Cu-Fe-MSNs | Dual metal-impregnated constructs | Janus-type | DOX | ~ 100 nm | Impregnating two similarly-charged metals facilitated shape changes and promoted the ROS-assisted CDT | [92] | |
| HMSNs-β-CD-AD-PEG |
Multiple surface-modified pH-responsive linkers, benzoic imine and boronic acid ester |
Spherical | DOX | ~ 100 nm | These PEG-coated, CD-gated, hollow MSNs with cascade pH stimuli cleaving the benzoicimine bonds and boronic acid ester presented excellent intracellular delivery | [431] | |
| M-CHO-DOX@DOX-PEG | pH-sensitive dynamic benzoic–imine covalent bond as capping | Spherical | DOX | ~ 160 nm | Dynamic PEGylation via benzoic–imine bond further endowed the drug-self-gated nanocarrier with tumor extracellular pH-triggered cell uptake and improved therapeutic efficiency in-vivo | [240] | |
| DOX-MSN-CF127 | Polymeric micelle (F127-CHO)-gating | Spherical | Curcumin, DOX | ~ 70 nm | Multifunctional stimuli-responsive opening of polymeric micelle cap improved the drug delivery and optical imaging | [432] | |
| MSN–R848 | Heterobifunctional cross-linker maleimide-PEG-NHS modified and biotin-avidin capped | Core–shell | R848 and OVAp | ~ 70 nm | The nanocomposites with pH-responsive acetal linker presented the release of R848 cargo and offered dendritic cells activation as well as enhanced cytotoxic T-cell responses | [256] | |
| MSN-PAA-PEG | Optimized degree of polymerization with escalated PAA unit number in PAA-PEG | Spherical | AZD6244 and PLX4032 | < 100 nm | The pH-responsive on-demand controlled release from MSNs reversed the MEK-inhibitor-induced suppression of activated CD8 + T-cells and enhanced the secretion of INF-γ and IL-2 | [255] | |
| MSN-Fe-AuNPs |
AuNPs-Cys as gatekeepers, pH-dependent photothermal conversion |
Core-satellite | DOX | ~ 100 nm | Fe-induced AuNPs presented combined photothermal therapy, chemotherapy, and Fenton reaction-based tumor therapy | [433] | |
| MSN-WS2-HP |
WS2QDs-HP, tLyP-1 |
Spherical cluster bomb | DOX | ~ 50 nm | The pH-responsive size-changeable constructs presented the CendR pathway and NIR-light-triggered photothermal ablation of 4T1 tumors | [434] | |
| Lipid-PEG coated silicasomes | Lipid bilayer and PEG-coated constructs for co-administration of anti-PD-1 antibody | Silicasome | DACHPt | ~ 140 nm | DACHPt silicasome by anti-PD-1 antibody presented excellent chemotherapy and ICD response in orthotopic Kras-derived pancreatic cancer | [262] | |
|
PEG and lipid bilayer coat A linked downstream cascade |
Core–shell silicasome | IRIN | < 100 nm | These composites with scale-up features presented improved therapeutic efficacy against robust treatment-resistant Kras-induced pancreatic cancer | [263] | ||
| USMO@MSNs | Ultrasmall manganese oxide-capping over MSNs | Core–shell structures | DOX | ~ 50 nm | The designed nanocomposites presented MRI-guided pH-switching theranostic performance for synchronous MRI diagnosis and chemotherapy | [435] | |
| GSH-responsive | MSN-S–S-NAC-Trp | Disulfide bond and short peptide as capping agents | Spherical | DOX | ~ 90 nm | A bolt-like blocking nanovalve presented GSH-responsive release for HeLa cell apoptosis | [291] |
| DMSN-DP@CM | MCF-7 membrane coated | Core/shell | DNA fuel strands | 243 nm | GSH-responsive DNA strands in DMSNs posed to Immune escape and homotypic-targeting | [364] | |
| MSNs-S–S-siRNA | Disulfide capping | Spherical | DOX and Bcl-2 siRNA | 80 nm | Synergistic tumor growth inhibition in-vivo showed potential chemotherapy and gene therapy | [292] | |
| CDs@MSN-TPP@AuNPs | TPP and AuNPs coated over the MSN surface | Spherical | DOX | ~ 40 nm | GSH-responsive etching of AuNPs provided effective cancer therapy and mitochondrial-targeted imaging | [436] | |
| MSN-ss-ADDA-TCPP | Disulfide-based Tat48-60, RGDS, ADDA, peptide-based amphiphile capping | Spherical | DOX | ~ 120 nm | Targeting and GSH-responsive delivery of DOX to αvβ3 integrin overexpressed tumor cells | [317] | |
| HMSNs | TEOS and BTESPD with disulfide linkages | Hollow mesoporous shell | DOX | ~ 100 nm | These constructs resulted in high loading capacity, and GSH-responsive controlled degradation | [293] | |
| Fa-PEG-MMSNs |
Fa-PEG coated Mn2+-doped MSNs |
Spherical | DHA | ~ 100 nm | Accumulating PL-PUFA-OOH oxidized by ·OH and destroyed the structure of polyunsaturated fatty acids | [437] | |
| Au@MSN@HP NPs | HA, HS, and HP glycosaminoglycan modification | Core–shell | DOX | ~ 100 nm | GSH-assisted degradation of the disulfide bond between GAG and MSNs favored precise synergistic chemophotothermal treatment | [438] | |
| PDA/MnO2 coated MSNs | PDA/MnO2 coating over MSNs | Spherical | DOX | 150–300 nm | GSH-assisted transformation of MnO2 to Mn2+ led to the release of drug cargo | [439] | |
| FMSN-MnO2-BCQ |
BSA-modified, NIR-II small molecule and MRI reporter |
Fusiform/rod-like | MnO2 and CQ4T | width- ~ 15 nm, length- ~ 90 nm | TME-activated tumor-deep delivery system for dual-mode imaging and self-reinforcing chemodynamic therapy | [440] | |
| Ultrasound-responsive | PV-MSNs | Platelet vesicles-coated over the surface | Spheroid | CA and IR780 | 100 nm | IR780-based SDT and the CA-based GSH depletion improved cancer ablation | [441] |
| MSN-FA-TAN-MB | FA-immobilized over the surface | MB | TAN | ~ 110 nm | This multifunctional vehicle showed exceptional ultrasound responsive properties towards tumor targeting and imaging | [442] | |
| FITC-labelled MSNs | Submicron cavitation nuclei | Spherical | Rhodamine B | – | Ultrasound-induced inertial cavitation enhanced the extravasation of the nanocarriers | [290] | |
| HYBRIDL-PEG-RGD | Biotin or RGD peptide coated | Spherical | DOX | ~ 220 nm | Ultrasound-responsive random copolymer enhanced cellular uptake and cancer-killing efficacy | [443] | |
| MSNs-PEG | PEG-coated over surface | Spherical | Gd(DTPA)2– | ~ 92 nm | MRgHIFU stimulated cargo release facilitated by ultrasound-responsive PEG for MRI-guided therapy | [444] | |
| MNP@MSNs-AMA-CD | Bulky hydrophilic β-CD capping | Core–shell | DOX | ~ 55 nm | HIFU-stimulated cleavage of ACVA C − N bonds facilitated the ultrasound-responsive release | [445] | |
| Magnetic-responsive | EuSPION@MSNs | Polarization anisotropy (r) of two luminescence emission bands | Core–shell | – | – | Néel relaxation as the dominant heating mechanism resulted in understanding hyperthermia-based drug release | [296] |
| SPNC@MSN | MnFe2O4@CoFe2O4 core and capped with Phe − Phe − Gly − Gly (N − C) | Core–shell | Fluorescein or daunorubicin | 120 nm | Localized magnetic heating presented high cytotoxicity on pancreatic carcinoma cells | [295] | |
| MMSNs-PEG | PEG and thermoresponsive polymer-coated over the surface | Core–shell | DOX | 160 nm | Heated magnetic species in the core facilitated the polymer transition and opening towards drug release from MSNs | [446] | |
| Fe3O4-mSiO2 | Janus | Janus-type | Berberine | ~ 300 nm | The superparamagnetic constructs with high drug-loading amounts, superior endocytic ability, and low cytotoxicity acted against hepatocellular carcinoma | [447] | |
| Mag@MSNs | Thermo-responsive polymer-coated core–shell MSNs | Core–shell | Fluorescein | 55 nm | These core–shell constructs avoided the risk of inducing tumor metastasis generated by hyperthermia | [294] | |
| SPION@MSN |
Retro-Diels Alder reaction DA, Mal, or CD |
Sphere | Fluorescein | 70–80 nm | Non-invasive external actuation through alternating magnetic fields improved the drug release | [448] | |
| MARS | ZnNCs Cucurbit[6]uril | Core–shell | DOX | < 200 nm | The non-invasive controlled delivery was achieved after being exposed to the AC field for treating breast cancer cells | [449] | |
| Temperature-responsive | THI@HMS@P(NIPAAm-MAA) | P(NIPAAm-co-MAA)-coated HMSNs | Hollow MSNs | THI | ~ 170 nm | The strongly temperature-dependent and distance-limiting mechanism was demonstrated using positive temperature coefficient pesticide | [450] |
| MSNs-MNFs | P(NIPAAm-co-HMAAm)-encapsulated with MET-MSNs | Spheres in the electrospun nanofibers | MET |
MSNs- < 100 nm MNFs-diameter of 420 nm |
ON–OFF’ switching of AMF showed excellent heat generation efficacy and subsequent cytotoxicity on B16F10 melanoma cells | [451] | |
| MSN-PEG | RAFT polymerization of PEG | Spherical | Sulforhodamine B, PDI | 140 nm | A temperature-controlled “pumping” mechanism was demonstrated for drug release from mesopores | [452] | |
| MSN-thermoresponsive polymer | Disulfide-containing cystamine linked thermoresponsive polymer | Spherical | DOX | 50–100 nm | UCST polymers coated over the surface presented responsive release against breast cancer cells (SK-BR-3) | [283] | |
| Light-responsive | Porphyrin capped-MSNs | Porphyrin capping | Spherical | RBP, TOP, or CAL | 130 nm | Visible radiation-assisted generation of ROS-cleavable linkages allowed the release of TOP | [277] |
| AuNPs-MSNs | AuNPs-capping with photoliable linker | Spherical | PTX | 100 nm | Low power photoirradiation-assisted cleavage of linkers facilitated the zero premature release for chemotherapy | [136] | |
| UCNPs@mSiO2-DPP–CD | Strong host–guest interactions between CD and Ad | Core–shell–shell | DOX and platinum(II) | 65 nm | Activating the platinum(IV), pro-drug gained higher toxicity effects of platinum(II) | [279] | |
| bMSNs-AZO/DS/CD-PMPC | AZO isomerization-modified surfaces | Core–shell | DS | 150 nm | Light-responsive drug delivery and lubrication enhancement were beneficial for the treatment of osteoarthritis | [281] | |
| CuS@MSNs | CuS coated with MSN over the surface | Core–shell | DOX | 86.2 nm | The carrier presented excellent combined NIR-based PTT and chemotherapy | [453] | |
| MSN-linker-azo/Ce6@Cargo@CD | CD-gated MSNs | Spherical | Rhodamine B or calcein | ~ 100 nm | Excellent spatiotemporal controllability of red light excitation and the active target ligand FA improved efficacy of PDT and chemotherapy and controlled drug release | [278] | |
| MC/IR820-MSNs | Thermal-sensitive hydrogel platform MC/IR820 | Hybrid hydrogel | DOX | ~ 50 nm | These versatile photo-responsive hydrogels offered synergistic chemophotothermal treatment of OSCC | [454] | |
| FITC-PGSN | Polyglycerol-doped MSNs | Spherical | (Rose bengal, RB) FITC | ~ 100 nm | TPA-PDT-assisted MSNs could transfer energy to the loading drugs via an intraparticle FRET mechanism | [455] | |
| FA-PEG–coated Ag-NPs-JNPs | FA-linked PEG-coated over the surface | Janus-type | ICG | 200–400 nm | The effector for photothermal therapy acted as the initiator to activate the chemotherapy | [269] | |
| Multi-responsive | MSN-S–S-DTPP&DTCPP | pH- and GSH-sensitivity | Spherical | DOX | ~ 120 nm | Versatile dual-stimuli-sensitive MSNs could provide an effective strategy for combinational tumor therapy | [456] |
| Serum albumin and myoglobin-gated UCNP@mSiO2 | pH, GSH, or H2O2-responsive | Core–shell spherical nanostructures with worm-like pores in shells | DOX | 64 nm | These nanocomposites showed spatiotemporally targeted drug delivery for cancer chemotherapy | [298] | |
| Dm@TMSN-PEI | Redox-enhanced pH-responsive | Spherical morphology with wormlike mesostructure | DOX and miRNA-145 | ~ 183 nm | The nanocomposites with affinity to glucose-regulated protein 78 (GRP78), a cell surface protein overexpressed in colorectal carcinoma is developed | [297] | |
| MSN-ANA-HFn | Redox- and pH-triggered | Spherical | DOX | 100 nm | HFn capped MSNs provided TfR1 targeting on suppression of tumor growth | [299] | |
| TTTMSNs |
pH- and redox-dual-responsive MSN-S–S-Peptide-MPEG |
Rectangular | DOX | ~ 125 nm | RGDFFFFC-assisted targeting, benzoic-imine bond-based pH-responsive, and di-sulfide cleavage-based redox-responsive enhanced the tumor-targeting efficacy | [457] | |
| MSN@p(NIPAAm-co-MA) |
Thermal- and pH-responsive p(NIPAAm-co-MA) |
Spherical | EVO and BBR | ~ 160 nm | These composites with dual drugs provided excellent therapeutic effects against EMT-6 mouse mammary carcinoma tumor allograft | [261] | |
| MSNs@PDA@keratin | pH and GSH dual responsive Keratin as capping | Spherical/ellipsoidal | DOX | ~ 100 nm | These composites selectively showed higher toxicity against A549 cells than normal cells | [301] | |
| MSN-SS-PDA | Redox/pH/NIR-multi-dependent, Disulfide linked PDA-coating | Spherical | DOX | ~ 130 nm | These composites exhibited excellent photo-thermal conversion ability, multi-stimuli responsive drug release, chemo/photothermal synergistic therapy effect | [458] | |
| MSN-S–S-N = C-HA |
pH- and redox-responsive HA-g-CD |
Sphere with highly ordered honeycomb channels | DOX | ~ 100 nm | The composites with dual-responsiveness provided CD44 over-expressed cancer cell targeting effects | [300] | |
| MSN-Au |
GSH- and NIR-triggered AuNPs |
Ellipsoid | DOX | ~ 250 nm | A combination of chemotherapy and photothermal therapy toward A549 cells | [302] |
β-CD: β-Cyclodextrin; ACVA: 4,4′-Azobis(4-cyanovaleric acid); AD- 1-Adamantanemethylamine; ADDA-TCPP: C12-CGRKKRRQRRRPPQRGDS; AMA: 1-Adamantylamine; AuNPs-Cys: L‐Cysteine‐derivatized gold nanoparticles; AZO: Azobenzene; BBR: Berberine; BFO: Bismuth ferrite; BTESPD: Bis[3-(triethoxysilyl)propyl] disulfide; CA: Cinnamaldehyde; CAL: Calcein; CDs: Carbon nanodots; Ce6: Chlorin e6; CendR: Neuropilin-1 (NRP-1)-dependent endocytic/exocytic transport; CM: Coumarin; CS-PtNPs@Zn-MSNs: Chitosan-Platinum nanoparticles coated Zinc-doped MSNs; CuS: Copper sulfide; Cu-Fe-MSNs Copper and iron-doped MSNs; DACHPt: Activated oxaliplatin (1,2-diamminocyclohexane platinum(II); DHA: Dihydroartemisinin; DMSNs-dendritic MSNs; DOX: Doxorubicin; DS: Diclofenac sodium; EVO: Evodiamine; EuSPION: Europium-doped superparamagnetic iron oxide nanoparticle; FA: Folate; FaPEG: Folate-grafted PEG; FCA-Fe3O4 coated carbon/silver; FITC: Fluorescein isothiocyanate; FRET: Fluorescence resonance energy transfer; Gd(DTPA)2–: Gadopentetate dimeglumine; GSH -glutathione; HA: Hyaluronic acid; HAp: Hydroxyapatite; Hfn: Human H chain ferritin; HMAAm: N-hydroxymethylacrylamide; HMSiO2 /HMSNs/HMS: Hollow mesoporous silica nanoparticles; HNPs: harmonic nanoparticles; HP: Heparin; HS: Heparin sulfate; HYBRID: Hybrid mesoporous silica nanocarrier; IBU: Ibuprofen; ICG: Indocyanine green; INF-Interferon; IL-Interleukin; JNPs: Janus-type MSNs; LB-MSN-OVA: Lipid bilayer-MSN-ovalbumin; MA: Methacrylic acid; Mal: Maleimidopropyl triethoxysilane 1; MARS: Magnetically activated release system; MB: Microbubble; MC: Methylcellulose; MET: Metformin; miRNA: MicroRNA; MMSNs: Manganese-doped MSNs; MNFs: Magnetic nanofibers; MNPs: MnFe2O4@CoFe2O4 nanoparticles; MRI: Magnetic resonance imaging; MRgHIFU: MRI-guided high-intensity focused ultrasound; mSiO2-mesoporous silica; MSNs- mesoporous silica nanoparticles; MSN-POLY: RAFT polymerization on the surface of MSNs; NIPAAm: N-isopropylacrylamide; OG: Oregon green; OSCC: Oral squamous cell carcinoma; OVAp: Ovalbumin; PAA: Polyacrylic acid; PDA: Polydopamine; PEG: Polyethylene glycol; PEI: Polyethylenimine; PGSN: Polyglycerol-doped MSNs; PL-PUFA-OOH: Lipid peroxides; PMPC: Poly(2-methacryloyloxyethyl phosphorylcholine); p(NIPAAm-co-MA) : Poly(N-isopropylacrylamide-co-methacrylic acid); PV: Platelet membrane vesicle; NAC: N-acetyl-l-cysteine; SDT: Sonodynamic therapy; siRNA: Small interfering RNA; SPNC: Superparamagnetic nanoparticle cores; TAN: Tanshinone IIA; TEOS: Tetraethyl orthosilicate; TfR1: Transferrin receptor 1; THI: Thiamethoxam; THPMP: 3-trihydroxysilyl propylmethylphosphonate; TOP: Topotecan; TPA-PDT: Two-photon activated-photodynamic therapy; TPP: Triphenylphosphine; Trp: Tryptophan; pDNA: Plasmid DNA; PV-coated MSNs: Platelet vesicles-coated MSNs; RB: Rose bengal; RBP: [Ru(bipy)3]Cl2; RITC: Rhodamine B isothiocyanate; ROS: reactive oxygen species; UCNPs: Upconversion nanoparticles; USMO: Ultrasmall manganese oxide; V7-RUBY: Wormhole mesoporous silica nanoparticles; YQRLGC: lysosomal sorting peptides; WS2-HP: Tungsten disulfide quantum dots; ZnNCs: Zinc-doped iron oxide nanocrystals