Table 1 Various advanced prototypes of MSNs conveying therapeutic cargo for various stimuli-responsive delivery

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]

HYBRID_L-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]