DataVXAdvanced MaterialsPaper
journal article·2025-01

Engineering Semiconducting Polymeric Nanoagonists Potentiate cGAS‐STING Pathway Activation and Elicit Long Term Memory Against Recurrence in Breast Cancer

Haitao Yuan, Chong Qiu, Xiaoxian Wang, Peili Wang, Letai Yi, Xin Peng, Xiaolong Xu, Wei Huang, Yunmeng Bai, Jinxi Wei, Jingbo Ma, Yin Kwan Wong, Chunjin Fu, Wei Xiao, Chunbo Chen, Ying Long, Zhijie Li, Jigang Wang

Advanced Materials· Volume 37· Issue 4
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Source abstract

Abstract

Abstract Triple‐negative breast cancer has an immunologically “cold” microenvironment, which leads to resistance to current immunotherapy. The activation of stimulator of interferon genes (STING) pathway has been thought a promising strategy to enhance immunotherapy efficacy. In this study, we adopted a comprehensive strategy that integrates innate immune responses with tumor‐targeting photothermal therapy (PTT) to simultaneously tackle multiple immune‐suppressive mechanisms in breast cancer. This semiconducting polymeric nanoagonists (DPTT‐Mn Lipo NPs) mediated PTT can effectively initiate tumor cell apoptosis and induce ICD, thereby reprogramming the immunosuppressive TME and activating STING. We confirmed the modulation of the TME through the PTT‐mediated ICD effect and the transactivation of the cGAS‐STING pathway in immune cells of the TME due to the released dsDNA via ICD, such as macrophages and DCs. Indeed, DPTT‐Mn Lipo NPs‐mediated PTT promoted M1 polarization of tumor‐associated macrophages, augmented T‐cell infiltration, facilitated dendritic cell (DC) maturation, and regulated type I interferon factor secretion, leading to efficient tumor suppression. Most importantly, the combination of DPTT‐Mn Lipo NPs‐based PTT with a checkpoint blockade therapy (anti‐PD‐1) can elicit long‐term immune memory besides tumor eradication. Collectively, this nano‐system can systemically activate antitumor immunity through STING activation and potentially establish long‐term memory against tumor recurrence.
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Research context

PolymersNanomaterials

OpenAlex topics: interferon and immune responses · Nanoplatforms for cancer theranostics · Immune cells in cancer

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

Affiliations

Department of Hyperbaric Oxygen Medicine Guangdong Provincial Clinical Research Center for Geriatrics Shenzhen Clinical Research Center for Geriatric Shenzhen People's Hospital The First Affiliated Hospital Southern University of Science and Technology Shenzhen Guangdong 518020 P. R. China

Center for Drug Research and Development Guangdong Provincial Key Laboratory of Advanced Drug Delivery System Guangdong Pharmaceutical University Guangzhou 510006 P. R. China

State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 P. R. China

National Clinical Research Center for Chinese Medicine Cardiology Xiyuan Hospital China Academy of Chinese Medical Sciences Beijing 100700 P. R. China

Inner Mongolia Medical University Hohhot Inner Mongolia 010000 P. R. China

Ningbo Municipal Hospital of TCM Affiliated Hospital of Zhejiang Chinese Medical University Ningbo 315010 P. R. China

Department of Critical Care Medicine Shenzhen People's Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of Southern University of Science and Technology Shenzhen 518020 P. R. China

Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Singapore 117600 Singapore

State Key Laboratory of Antiviral Drugs School of Pharmacy Henan University Kaifeng 475004 P. R. China

Funding

Shenzhen Science and Technology Innovation Program · National Natural Science Foundation of China · Science and Technology Foundation of Shenzhen City

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