1. Academic Validation
  2. Engineered Apoptosis-Bioinspired Nanoparticles Initiate Immune Cascade for Cancer Immunotherapy of Malignant Ascites

Engineered Apoptosis-Bioinspired Nanoparticles Initiate Immune Cascade for Cancer Immunotherapy of Malignant Ascites

  • ACS Appl Mater Interfaces. 2023 Feb 14. doi: 10.1021/acsami.2c19769.
Anmin Huang 1 2 3 Feixia Guo 2 Zhijie Yu 4 Pixu Liu 1 Shiying Dong 1 3 Yunjie Zhang 1 3 Yifan Kong 1 3 Xiuyan Kong 1 3 Ting Li 3 Yongde Luo 5 Hongping Xia 6 Keqing Shi 2 Jinglin Xia 1 7 8
Affiliations

Affiliations

  • 1 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, China.
  • 4 Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 5 The First Affiliated Hospital & School of Pharmacological Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 6 Zhongda Hospital, School of Medicine & Advanced Institute for Life and Health, Southeast University, Nanjing 210009, China.
  • 7 Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 8 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Abstract

Malignant ascites (MA) is a common symptom of peritoneal metastasis in liver Cancer. Cancer Immunotherapy can modulate immune cells to induce antitumor immune efficiency. Reprogramming tumor immune microenvironment (TIME) is a momentous strategy to overcome immunosuppression and achieve immune functional normalization. Inspired by the inherent apoptotic bodies and vesicles, we proposed and systematically studied engineered apoptosis-bioinspired nanoparticles (EBN) for Cancer Immunotherapy of MA. Using both in vitro and in vivo experimental validations, we elucidated that EBN could be efficiently engulfed by the tumor-associated macrophages (TAMs) and manipulate their polarization. Moreover, a boosted immune cascade response as a result of heightening cytotoxic T-lymphocytes (CTLs) activity was investigated. Based on these results, EBN was confirmed to have strong immune cascade activation capability. Remarkably, the injection of EBN further reduced ascites volume and reformed immune cell subtypes, compared to the injection of either PBS or free TMP195 alone. In short, this novel nanodrug delivery system (NDDS) represents a prospective immunotherapeutic approach for clinical therapeutics of hepatoma ascites and other malignant effusion.

Keywords

Cancer immunotherapy; Malignant ascites; Nanodrug delivery system; Tumor immune microenvironment; Tumor-associated macrophage.

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