Boosting Antitumor Immunity via a Tumor Microenvironment‐Responsive Transformable Trifecta Nanovaccine

Author:

Li Qiang1ORCID,Dang Meng2,Tao Jun2,Li Xiaoye1,Xiu Weijun3ORCID,Dai Zhuo1,He Ao1,Ding Meng1,Zhang Yu1ORCID,Wen Zhi‐fa4,Su Xiaodan2,Elbourne Aaron James5ORCID,Bao Lei5ORCID,Chen Lin1,Mou Yongbin1ORCID,Teng Zhaogang2ORCID,Dong Heng1ORCID

Affiliation:

1. Nanjing Stomatological Hospital Affiliated Hospital of Medical School Nanjing University 30 Zhongyang Road Nanjing Jiangsu 210008 China

2. Key Laboratory for Organic Electronics and Information Displays Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials Jiangsu National Synergetic Innovation Centre for Advanced Materials Nanjing University of Posts and Telecommunications 9 Wenyuan Road Nanjing Jiangsu 210023 China

3. Institute for Health Innovation and Technology Biomedical Engineering Department National University of Singapore 21 Lower Kent Ridge Road Singapore 119276 Singapore

4. Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital 123 Tianfei Lane, Mochou Road Nanjing Jiangsu 210004 China

5. School of Science Royal Melbourne Institute of Technology (RMIT) University 124 La Trobe Street Melbourne VIC 3000 Australia

Abstract

AbstractIn situ tumor vaccines (ISTVs) hold great potential in tumor immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T‐cell immune responses, and stubborn immunosuppressive tumor microenvironment (TME), still need to be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME‐responsive transformable ability is developed to tri‐boost antitumor immunity. First, sufficient endogenous tumor‐associated antigens (TAAs) are liberated in situ after immunogenic cell death is induced via TriNV‐based photoimmunotherapy. In the TME, soft‐transformed TriNV improves the uptake of TAAs by DCs to enhance acquired immunity. Second, the self‐adjuvating TriNV and the TME‐responsive released Mn2+ synergistically promote DC maturation and macrophage M1 polarization by augmenting the stimulator of interferon genes activation to further amplify T‐cell immune responses. Moreover, the decomposition of MnO2 within the core of TriNV exhausts glutathione and facilitates O2 release to alleviate hypoxia in the TME, thereby overcoming the chemical obstacles of the TME to further mitigate immunosuppression. Thus, TriNV remarkably eradicates primary tumors and inhibits distant metastasis, thus demonstrating great potential as a feasible and effective ISTV nanoplatform for combating poorly immunogenic solid tumors.

Funder

Natural Science Foundation of Jiangsu Province

Jiangsu Provincial Key Research and Development Program

Nanjing Medical Science and Technique Development Foundation

Publisher

Wiley

Subject

Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials

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