Table 1.
Summary of TME‐responsive nanomedicine for cancer immunotherapy
| Delivery platform | Immunotherapeutic drug | Sensitive molecules/bond | Source |
|---|---|---|---|
| pH‐responsive nanomedicine | |||
| Galactosyl dextran‐retinal (GDR) nanogels | OVA | Hydrazine bond | [23] |
| DEX–HAase nanoparticles | 3‐(bromomethyl)‐4‐methyl‐2,5‐furandione | [24] | |
| PCL–Hyd–PEG vesicles | Antigens HCP, adjuvants CpG ODN | PCL–Hyd–PEG | [25] |
| Dendrigraft poly‐l‐lysines | Zoledronic acid (ZA) | 1,6‐Bis(4‐formylbenzoyloxy) hexane | [26] |
| RPTDH NPs | R848 | Poly‐l‐histidine (PHis) | [27] |
| Poly(ethylene glycol)‐block‐poly(diisopropanol amino ethyl methacrylate‐co‐hydroxyethyl methacrylate) (PDPA)–PPa | Small interfering RNA (siRNA) | OEI‐C14 | [28] |
| PCPP hybrid micelles | PD‐L1‐blockade siRNA, MTPP(PS) | Amide bond | [29] |
| Nanogels | PTX, IL‐2 | Chitosan polymers | [30] |
| CaCO3 matrix | CpG ODNs, IDOi, Ca2+ | CaCO3 | [31] |
| H‐MnO2 nanoshells | Ce6, DOX | H‐MnO2 | [32] |
| Poly(ethylene glycol)‐block‐poly(D,L‐lactide) (PEG‐b‐PLA) NPs | CDNs | cytosine (C) | [33] |
| pHLIP | [34] | ||
| Hollow silica nanoparticle | Catalase, Ce6 | [35] | |
| PDPM NPs | OVA | PDPA tertiary amino groups | [36] |
| PD‐L1 binding peptide conjugate (DCS) NPs | DOX, D‐PPA | Maleic acid amide bond | [37] |
| Sensitive cluster nanoparticles (SCNs) | 1. 4‐[2((1R,2R)‐2‐Hydroxycyclohexylamino)‐benzothiazol‐6‐yloxyl]‐pyridine‐2‐carboxylic acid methylamide (BLZ‐945), Pt‐based prodrug | Hydrophobic–hydrophilic transition | [38] |
| STING‐NPs | Cyclic guanosine monophosphate‐adenosine monophosphate (cGAMP) | Polymersomes | [39] |
| Mesoporous silica nanoparticles (MSNPs) | Mitogen‐activated protein kinase kinase inhibitors (MEKi) | Anionic polymer polyacrylic acid | [40] |
| MnO2 particles | IPI549 | MnO2 | [41] |
| Hierarchical‐responsive nanoconjugates (HRNs) | Docetaxel (DTX) | P(C7A‐r‐DTX) block | [42] |
| AuNPs | DOX, hydroxychloroquine (HCQ) | HCQ prodrug | [43] |
| Human serum albumin | DOX prodrug | 2,3‐Dimethylmaleic amide bond | [44] |
| Mannose‐modified PEGylated poly(lactic‐co‐glycolic acid) (MAN‐PEG‐PLGA) | Tumor associated antigens (TAA) | Hydrazone bond | [45] |
| poly(l‐histidine), HA | R848, DOX | Hydrazone bond | [46] |
| Micelleplexes | siRNA–PD‐L1 | GA, C7A, DPA, C4A | [47] |
| Metal‐organic frameworks (MOFs) | TAAs, CpG ODNs | Lanthanide ions and GMP | [48] |
| GSH‐responsive nanomedicine | |||
| HA–CD | PPa, JQ1 | Disulfide bond | [49] |
| Redox‐activatable liposome (RAL) | PPa, IDO inhibitor | Disulfide bond | [50] |
| Polysaccharide fucoidan and polyamide‐amine (PAMAM) dendrimer | Verteporfin (VP), MnO2 NPs | Disulfide bond | [51] |
| Ds‐sP NPs | PS TCPP‐TER | Disulfide bond | [52] |
| Biodegradable mesoporous silica nanoparticles (bMSN) | CpG ODN, Ce6 | Disulfide bond | [53] |
| Hollow mesoporous organosilica nanoparticles (HMONs) | HCPT, siMCT‐4 | Disulfide bond | [54] |
| Copolymer nanoparticles | SN38, DMXAA | Disulfide bond | [55] |
| Protein nanogel | Disulfide bond | [56] | |
| Light‐inducible nanocargo (LINC) | PPa, NLG919, OXA | Disulfide bond | [57] |
| HCNSP nanovector | PPa, NLG919 | Disulfide bond | [58] |
| polyacrylic acid (PAA)–polyethyleneimine (PEI) 600 | OVA | Disulfide bond | [59] |
| N′‐bis(acryloyl)cystamine (BISS) | Cisplatin prodrug, IR820, DTX | Ester bond | [60] |
| HA nanohydrogel | Oncolytic viruses (OVs) | Disulfide bond | [61] |
| Human serum albumin | PTX, siPD‐L1 | Disulfide bond | [62] |
| ROS‐responsive nanomedicine | |||
| 3s‐PLGA–PEG NPs | OVA | Peroxalate ester bond | [63] |
| 3s‐PLGA–PO–PEG/PEI | OVA | Peroxalate ester bond | [64] |
| Albumin | aPD1, aCD47 | bis‐N‐hydroxy succinimide modified 2,2′‐[propane‐2,2‐diylbis(thio)]diacetic acid (NHS–IE–NHS) | [65] |
| Polypeptide‐based gel | aPD‐L1, D‐1MT | l‐Methionine (Me) and D‐1MT | [66] |
| Hydrogel | aPD‐L1, GEM | TSPBA | [67] |
| Aspirin polymeric | 4‐formylbenzeneboronic acid | [68] | |
| T7‐PEG–N,N,N‐Trimethyl chitosan(TMC)–4‐nitrophenyl‐4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzyl carbonate(NBC) NPs | siRNA–PD‐L1, DOX | T7‐PEG‐TMC‐NBC | [69] |
| Hypoxia‐responsive nanomedicine | |||
| Mesoporous silica | CpG ODN, Ce6 | Azobenzene linker | [70] |
| Phthalocyanine derivative | AQ4N | AQ4N | [71] |
| MFNs | DOX | polypropylene oxide‐b‐ poly(6‐(2‐nitroimidazol‐1‐yl)hexyl methacrylate) (PEO‐b‐PNIHM) | [72] |
| mPEG–poly(γ‐propargyl‐L‐ glutamate (PPLG) | DOX | p‐Aminobenzyl groups | [73] |
| Enzyme‐responsive nanomedicine | |||
| mPEG–Pep–IDOi | IDO inhibitor, ICG | mPEG–Pep–IDOi | [74] |
| MSNs | DOX | Peptide substrate of MMPs | [75] |
| Triglycerol monostearate | DOX | Triglycerol monostearate (TGM) | [76] |
| Poly(ethyleneglycol)‐b‐poly(L‐lysine) (PLL)–1‐mt, HA–Ce6 | aPD‐L1, Ce6, 1‐mt | Hyaluronic acid–Ce6 | [77] |
| Triphenylphosphine‐modified‐poly(L‐lactic acid) (TPT polymer) | DOX, d‐LND | HA–DOX | [78] |
| DNA nano‐cocoons (DNCs) | aPD1, CpG ONDs | Single‐stranded DNA, TGM | [79] |
| IR780‐M‐APP NPs | APP | MMP‐2 cleavable peptide sequence | [80] |
| ATP‐responsive nanomedicine | |||
| CpG–cApt | CpG ODN, Ca2+ | ATP‐specific aptamer | [81] |
| PCL–PEI–PBA | PD‐L1 siRNA, IR780 | PBA | [82] |
| Multiresponsive nanomedicine | |||
| BCPN | OXA prodrug, NLG919 | Disulfide bond, PEGylated OXA prodrug | [83] |
| PEG–2‐propionic‐3‐methylmaleic anhydride (CDM)–PEI–P(CURDT) | Curcumin, NLG919 | Disulfide bonds, CDM | [84] |
| Nanoparticle assembled from DEAP molecule | PD‐L1 antagonist, NGL919, and a substrate peptide of MMP‐2 | DEAP molecule, peptide substrate of MMP‐2 | [85] |
| Azide–PEG–PAsp | aPD‐1, PTX | MMP‐2 sensitive peptide linker, acid‐labile bond | [86] |
| BRNPs | d‐SN38, d‐LND | PEGylated bilirubin, d‐SN38, d‐LND, disulfide bond | [87] |