DataVXAdvanced MaterialsPaper
journal article·2024-02

Tumor Microenvironment‐Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy

Dan Liu, Shuang Liang, Kongshuo Ma, Qian‐Fang Meng, Xingang Li, Jian Wei, Mengli Zhou, Kaiqing Yun, Yuanwei Pan, Lang Rao, Xiaoyuan Chen, Zhaohui Wang

Advanced Materials· Volume 36· Issue 6
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Source abstract

Abstract

Abstract Insufficient activation of the stimulator of interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits the effect of cancer immunotherapy. Herein, tumor microenvironment (TME)‐responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING and Toll‐like receptor 4 (TLR4) to augment STING activation via TLR4‐mediated nuclear factor‐kappa B signaling pathway stimulation, leading to the increased secretion of type I interferons (i.e., 4.0‐fold enhancement of IFN‐β) and pro‐inflammatory cytokines to promote a specific T cell immune response. Moreover, PMM NPs relieve the immunosuppression of the TME by decreasing the percentage of regulatory T cells, and polarizing M2 macrophages to the M1 type, thus creating an immune‐supportive TME to unleash a cascade adaptive immune response. Combined with an anti‐PD‐1 antibody, synergistic efficacy is achieved in both inflamed colorectal cancer and noninflamed metastatic breast tumor models. Moreover, rechallenging tumor‐free animals with homotypic cells induced complete tumor rejection, indicating the generation of systemic antitumor memory. These TME‐responsive nanoparticles may open a new avenue to achieve the spatiotemporal orchestration of STING activation, providing a promising clinical candidate for next‐generation cancer immunotherapy.
Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: interferon and immune responses · Immune cells in cancer · Ubiquitin and proteasome pathways

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

Affiliations

State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China

Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China

Institute of Biomedical Health Technology and Engineering Shenzhen Bay Laboratory Shenzhen 518132 China

Department of Pharmacy Beijing Friendship Hospital Capital Medical University Beijing 100050 China

Department of Interventional Radiography Beijing Friendship Hospital Capital Medical University Beijing 10050 China

Department of Diagnostic Radiology Nanomedicine Translational Research Program Yong Loo Lin School of Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 119074 Singapore

Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering College of Design and Engineering National University of Singapore Singapore 119074 Singapore

Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore

Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) 61 Biopolis Drive, Proteos Singapore 138673 Singapore

Funding

National Natural Science Foundation of China · Fundamental Research Funds for the Central Universities · National University of Singapore · National Medical Research Council · National Research Foundation

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