DataVXAdvanced Functional MaterialsPaper
journal article·2024-01Open access

A Chemoimmunotherapy Nanogel Enables Efficient Delivery of Interleukin‐2 and Induction of Immunogenic Cell Death for Effective Cancer Therapy

Hsuan‐Yu Mu, Yen‐Nhi Ngoc Ta, Max Jing Rui Tham, Fu‐Fei Hsu, Yu‐Chieh Lin, Hsi‐Chien Huang, Yun‐Chieh Sung, Chih‐I Huang, Ching‐Ling Wu, Chao‐Hung Chang, Sheng Yang, Tsung‐Ying Lee, Dehui Wan, Jane Wang, Dan G. Duda, Yves Boucher, Jen‐Huang Huang, Wee Han Ang, Yunching Chen

Advanced Functional Materials· Volume 34· Issue 1
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Source abstract

Abstract

Abstract Interleukin‐2 (IL‐2) is one of the first FDA‐approved immunotherapeutics, but its use is limited by toxicity and low efficacy. In addition, all immunotherapies are limited by the immunosuppressive and desmoplastic microenvironment of “immunologically cold” tumors, such as pancreatic ductal adenocarcinoma (PDAC) or hepatocellular carcinoma (HCC) with advanced liver fibrosis. Here, a new chemoimmunotherapy nanogel (IL2‐Pt@Nanogel) for dual delivery of IL‐2 and the type II immunogenic cell death inducer Pt‐NHC that reduces the immunosuppressive phenotype of tumor‐associated macrophages and diminishes regulatory T cell infiltration by inducing the production of type I interferon (IFN) by cancer cells is reported. Combining the angiotensin II receptor blocker losartan with IL2‐Pt@Nanogel treatment reduces desmoplasia and reprogrammes the microenvironment of PDAC and HCC toward an immunostimulatory one. These effects result in potent anti‐tumor efficacy in models of primary and metastatic PDAC and HCC with underlying liver fibrosis. This study presents a strategy for IL‐2‐based chemoimmunotherapy with the potential for clinical translation to treat solid tumors.
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Research context

Nanomaterials

OpenAlex topics: Immune cells in cancer · Cancer Immunotherapy and Biomarkers · Phagocytosis and Immune Regulation

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

Affiliations

Institute of Biomedical Engineering National Tsing Hua University Hsinchu 30013 Taiwan

Department of Chemical Engineering National Tsing Hua University Hsinchu 30013 Taiwan

International Intercollegiate Ph.D. Program National Tsing Hua University Hsinchu 30013 Taiwan

Department of Chemistry National University of Singapore Singapore 117544 Singapore

NUS Graduate School for Integrative Sciences and Engineering National University of Singapore Singapore 119077 Singapore

Institute of Biomedical Sciences Academia Sinica Taipei 11529 Taiwan

Steele Laboratories for Tumor Biology Department of Radiation Oncology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA

Department of Chemistry National Tsing Hua University Hsinchu 30013 Taiwan

Funding

National Health Research Institutes · Ministry of Education · National Institutes of Health · U.S. Department of Defense · Ministry of Science and Technology

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