Table 4 Comprehensive comparative analysis of nanomaterials for reversing the TME
From: Nanomaterials-driven in situ vaccination: a novel frontier in tumor immunotherapy
Nanomaterial Type | Key Features | Mechanism of Action in TME | Efficacy | Safety Profile | Clinical Translation Potential | Challenges | Examples/References |
|---|---|---|---|---|---|---|---|
Naturally Derived | Biocompatible, immunogenic; derived from biological sources such as plant viruses or bacteria | Activates immune cells (e.g., DCs, TLRs); enhances cytokine secretion | Moderate; context-dependent; effective in preclinical tumor models | High biocompatibility; low systemic toxicity | Limited; primarily in early-stage research; promising preclinical data | Batch-to-batch variability; difficulty in standardizing source material; scalability issues | Cowpea mosaic virus (CPMV) induces TLR2, TLR4, TLR7 activation; studies in melanoma and breast cancer models |
Inorganic | Stable; customizable; high payload capacity | Modulates hypoxia, generates ROS, improves T cell infiltration | High; excels in reversing hypoxic TME and delivering adjuvants | Risk of long-term toxicity; potential for bioaccumulation | Some approved agents (e.g., hafnium oxide in NBTXR3); ongoing clinical trials | Reproducibility in size, shape, and coating; toxicity concerns; limited clearance in vivo | Gold NPs enhance T cell infiltration; silica NPs induce DAMP release; clinical applications in sarcoma (NBTXR3) |
Liposomal | Biocompatible; customizable; FDA-approved delivery platform | Delivers cytokines, adjuvants, or chemotherapy agents; enhances ICD | High; established efficacy in clinical settings (e.g., Doxil) | Excellent safety profile; minimal immunogenicity | Strong; multiple FDA-approved formulations for cancer | Stability issues during storage; cost-intensive encapsulation processes | Liposomal CpG combined with cisplatin for enhanced T cell activation and ICD |
Polymer-Based | Flexible; adaptable for multiple payloads; biodegradable | Reprograms macrophages; delivers siRNA, adjuvants, or ICD inducers | High; tunable for specific therapeutic needs | Moderate to high; some formulations show immunogenicity | Emerging; ongoing clinical trials for cancer immunotherapy | Complex synthesis; scalability limitations; potential inflammatory response | Polyethylene glycol-PLGA with doxorubicin; siRNA delivery for DC activation |
Chitosan | Unique bioadhesive and immunostimulatory properties | Stimulates T cells and NK cells; enhances DC maturation | Moderate to high; potent in preclinical tumor models | High; biocompatible; low toxicity | Early-stage research; limited clinical examples | Chemical instability; limited drug-carrying capacity; narrow applications | Chitosan-coated hollow CuS NPs for photothermal therapy combined with immunotherapy |
Mixed Organic/Inorganic | Combines advantages of organic (biocompatibility) and inorganic (stability, targeting) systems | Synergistically enhances ICD and immune activation; improves payload delivery | High; synergistic effects enhance immune response | Context-dependent; toxicity varies with formulation | Emerging; limited clinical examples but strong experimental potential | Manufacturing complexity; higher costs; potential for combined toxicity from organic/inorganic materials | PLGA-PEG combined with iron oxide for ICD and TME modulation; fibrin gel encapsulating calcium carbonate nanoparticles |