Article Figures & Data
Figures
- Figure 1
(A) Schematic diagram of the characteristics of “hot” tumors and “cold” tumors. (B) Size-optimized nanoparticles accumulate within tumors via the EPR effect. (C) Nanoparticles can combine multiple therapeutic drugs with distinctly different properties for co-delivery to tumor sites. (D) Nanoparticles may be engineered to interact synergistically with multiple drugs and external energy sources, thereby enhancing immunogenic cell death (ICD).
- Figure 2
(A) Schematic diagram of TME characteristics, including low pH, enzyme overexpression, redox imbalance, ATP overexpression, hypoxia, and immunosuppressive microenvironment. (B) Schematic diagram of the TME-responsive polymeric nanoparticles response module.
Tables
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
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