Acidity-responsive polyphenol-coordinated nanovaccines for improving tumor immunotherapy via bidirectional reshaping of the immunosuppressive microenvironment and controllable release of antigens

• Published in: Biomaterials science Vol. 12; no. 12; pp. 3175 - 3192
• Main Authors: Qiu, Huimin, Wang, Shuman, Huang, Rimei, Liu, Xingyu, Li, Liqun, Liu, Zheng, Wang, Aihui, Ji, Shichen, Liang, Hong, Jiang, Bang-Ping, Shen, Xing-Can
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 11.06.2024
• Subjects: Ablation; Animals; Antigens; Cancer Vaccines - administration & dosage; Cancer Vaccines - chemistry; Cancer Vaccines - immunology; Cell Line, Tumor; Controllability; Coordination; Effectiveness; Ferric Compounds - chemistry; Hydrogen-Ion Concentration; Imines; Immune system; Immunotherapy; Lymphocytes; Macrophages; Mice; Mice, Inbred C57BL; Nanoconjugates - chemistry; Nanoparticles - chemistry; Nanovaccines; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - chemistry; Ovalbumin - immunology; Polyphenols - chemistry; Polyphenols - pharmacology; Schiff Bases - chemistry; Tannic acid; Tannins - chemistry; Tannins - pharmacology; Tryptophan - analogs & derivatives; Tryptophan - chemistry; Tumor Microenvironment - drug effects; Tumors
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d4bm00490f

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared a Schiff base reaction. Fe was coordinated with TA-OVA to produce a Fe -TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between Fe and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.