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

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 micro -environment (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 immunother-apy 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.

Automated summary

Malignant ascites is a common symptom of peritoneal metastasis in liver cancer, and cancer immunotherapy can modulate immune cells to induce antitumor immune efficiency. In this study, engineered apoptosis-bioinspired nanoparticles (EBN) were proposed and studied for cancer immunotherapy of malignant ascites. Through in vitro and in vivo experimental validations, EBN was found to efficiently engulf tumor-associated macrophages (TAMs) and manipulate their polarization, leading to an enhanced immune cascade response. Furthermore, injection of EBN reduced ascites volume and reformed immune cell subtypes compared to other treatments.