journal article·2024-02Open access

STING Agonist‐Loaded Nanoparticles Promotes Positive Regulation of Type I Interferon‐Dependent Radioimmunotherapy in Rectal Cancer

Lei Wang, Han Zhou, Qingjing Chen, Zhiwen Lin, Chenwei Jiang, Xingte Chen, Mingdong Chen, Libin Liu, Lingdong Shao, Xiaolong Liu, Jianji Pan, Jingcheng Wu, Jibin Song, Junxin Wu, Da Zhang

Advanced Science· Volume 11· Issue 7

Abstract

Abstract Hypoxia‐associated radioresistance in rectal cancer (RC) has severely hampered the response to radioimmunotherapy (iRT), necessitating innovative strategies to enhance RC radiosensitivity and improve iRT efficacy. Here, a catalytic radiosensitizer, DMPtNPS, and a STING agonist, cGAMP, are integrated to overcome RC radioresistance and enhance iRT. DMPtNPS promotes efficient X‐ray energy transfer to generate reactive oxygen species, while alleviating hypoxia within tumors, thereby increasing radiosensitivity. Mechanistically, the transcriptomic and immunoassay analysis reveal that the combination of DMPtNPS and RT provokes bidirectional regulatory effects on the immune response, which may potentially reduce the antitumor efficacy. To mitigate this, cGAMP is loaded into DMPtNPS to reverse the negative impact of DMPtNPS and RT on the tumor immune microenvironment (TiME) through the type I interferon‐dependent pathway, which promotes cancer immunotherapy. In a bilateral tumor model, the combination treatment of RT, DMPtNPS@cGAMP, and αPD‐1 demonstrates a durable complete response at the primary site and enhanced abscopal effect at the distant site. This study highlights the critical role of incorporating catalytic radiosensitizers and STING agonists into the iRT approach for RC.
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Research context

OpenAlex topics: interferon and immune responses · Cancer Immunotherapy and Biomarkers · Cancer, Hypoxia, and Metabolism

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation Oncology Fujian Cancer Hospital Fujian Medical University Fuzhou 350025 P. R. China

Department of Oncology the Second Affiliated Hospital of Nanchang University Nanchang 360000 P. R. China

Department of Clinical Oncology The University of Hong Kong‐Shenzhen Hospital Shenzhen Guangdong 518053 P. R. China

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. China

Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Fujian Medical University Fuzhou 350004 P.R. China

School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 P. R. China

Department of Radiation Oncology Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. China

CAS Key Laboratory of Design and Assembly of Functional Nanostructures Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou 350002 P. R. China

Mengchao Med‐X Center Fuzhou University Fuzhou 350116 P. R. China

Department of Health Science Technology and Education National Health Commission of the People's Republic of China Beijing 100088 China

State Key Laboratory of Chemical Resource Engineering College of Chemistry Beijing University of Chemical Technology Beijing 10010 P. R. China

Funding

China Postdoctoral Science Foundation

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