Summary of TME-responsive polymeric nanoparticles enhancing cancer immunotherapy
| Response type | Polymer formulation | Loaded medication | Therapeutic model | Therapeutic outcomes | Ref. |
|---|---|---|---|---|---|
| pH response | PBA modified poly(ethylene glycol)-b-poly(ε-caprolactone) (PBA-PEG-b-PCL); poly(ε-caprolactone)-b-poly(β-amino ester) (PCL-b-P(D)AE) | Interleukin (IL)-12 | Mouse melanoma: large advanced tumors, primary and distant model, lung metastasis model | This system demonstrated significant inhibitory effects on melanoma, produced a distant effect, and suppressed postoperative tumor recurrence and metastasis. | 10 |
| COOH-PEG-b-PCL; PCL-b-PAE | Chemokine (CXCL)-9; BRD4-PROTAC (dBET6) | Mouse breast cancer model | CXCL9 and dBET6 synergistically enhanced T-cell-dependent antitumor immunity by promoting CD8+ T-cell infiltration and inducing programmed cell death. | 11 | |
| Enzyme response | Dual-sensitive nanoparticle (Dual-NP) system composed of VPLSLYSG-modified dendrimer and dextran nanoparticles | DOX | Mouse glioblastoma model | Within the glioblastoma model, the dual-NPs exhibited exceptional deep tumor penetration and a retention period extending to 6 days. | 12 |
| Photosensitizer was conjugated with methoxy poly(ethylene glycol) via GALGLPG (mPEG-GALGLPG-PPa) | Indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor | CT26 colorectal and 4T1 breast mouse models | Compared with photodynamic therapy alone, this combined immunotherapy regimen demonstrated significantly enhanced antitumor efficacy. | 13 | |
| ROS response | PPCD, CpG/PAMAM-TK-Ad, mPEG-TK-Ad | Pt (IV), CpG | Mouse colorectal model | This system promoted antigen-presenting cell activation, antigen presentation, and robust antitumor immune responses. | 14 |
| GSH response | Phosphorus dendrimer-copper(II) complexes (1G3-Cu), PCL-SS-PEG | Toyocamycin (Toy) | Mouse melanoma model | This nanoparticle eradicated tumors and suppressed recurrence and metastasis by synergistically inducing ICD through dual mitochondrial/endoplasmic reticulum pathway. | 15 |
| Hypoxia response | PNBJQ | Immunomodulating agent JQ1 | Mouse colorectal model | PNBJQ responded to tumor hypoxia to overcome innate and adaptive immune resistance by triggering ICD and downregulating PD-L1 under near-infrared light irradiation. | 16 |
| ATP response | ALG-Aapt/CpG | Oxaliplatin, CpG | CT26 colorectal model | Smart hydrogels released immune adjuvants concurrently with low-dose repeated chemo/radiotherapies to enhance antitumor immune responses. | 17 |
| E. coli@PDMC-PEG | Mn2+ | Mouse subcutaneous melanoma, rabbit in situ liver cancer | This system was degraded in an ATP-excessive TME, synergistically activating the cGAS-STING pathway by releasing Mn2⁺ and exposing bacteria, thereby effectively inhibiting tumor growth. | 18 | |
| Multiple responses | mPEG-b-P(MTE-co-PDA) | Niclosamide | Murine triple-negative breast cancer and syngeneic oral cancer models | ROS/pH dual-responsive MPNPs combined with oncolytic viruses enhanced tumor penetration, induced pyroptosis, and stimulated antitumor immunity. | 19 |
| COOH-PEG-PAEMA | Fe2O3, DOX | 4T1 breast mouse model | This triple-responsive nanoplatform accumulated in tumor tissue, enhanced ICD, and promoted T-cell proliferation. | 20 |