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

被引：1

作者：

Qiu, Huimin ^{[1
]}

Wang, Shuman ^{[1
]}

Huang, Rimei ^{[1
]}

Liu, Xingyu ^{[1
]}

Li, Liqun ^{[1
]}

Liu, Zheng ^{[1
]}

Wang, Aihui ^{[1
]}

Ji, Shichen ^{[1
]}

Liang, Hong ^{[1
]}

Jiang, Bang-Ping ^{[1
]}

Shen, Xing-Can ^{[1
]}

机构：

[1] Guangxi Normal Univ, Collaborat Innovat Ctr Guangxi Ethn Med, Collaborat Innovat Ctr Guangxi Ethn Med, Key Lab Chem & Mol Engn Med Resources,State Key La, Guilin 541004, Peoples R China

来源：

BIOMATERIALS SCIENCE | 2024年 / 12卷 / 12期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1039/d4bm00490f

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

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 via a Schiff base reaction. Fe(III )was coordinated with TA-OVA to produce a Fe-III-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-III 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.

引用

页码：3175 / 3192

页数：18