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

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.

Ferroptosis‐Enhanced Immunotherapy with an Injectable Dextran‐Chitosan Hydrogel for the Treatment of Malignant Ascites in Hepatocellular Carcinoma

“…[ 58 , 59 ] Several studies have attempted to establish engineered nanoparticles for the repolarization of TAMs or direct cytotoxicity of tumor cells in mouse models of malignant ascites. [ 59 , 60 , 61 ] However, therapeutic regimens often required consecutive daily intraperitoneal administration for 1–2 weeks and were nearly incurable. Importantly, while frequent administration is essential to maintain high effective concentrations in the peritoneal cavity, it could lead to extra pain and infection risk for patients.…”

Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy

“…Gram-negative bacterial outer membrane vesicles (OMVs), enriched with outer membrane proteins, are being explored as adjuvants or vaccines due to their immunogenicity, a favorable safety profile, and stability. OMVs can specifically interact with DCs via polysaccharide-TLR2, stimulating regulatory T cells and cytokine production [ 105 ]. Moreover, OMVs can activate APCs by delivering bacterial peptides through internalization by epithelial cells [ 106 ].…”

Immunotherapy for Peritoneal Carcinomatosis: Challenges and Prospective Outcomes

“…In fact, injecting the EBNs resulted in a greater reduction in ascites volume and a shift in immune cell subtypes compared to injections of either PBS or free TMP195 alone. Overall, this new nanodrug delivery system (NDDS) presents a promising immunotherapeutic approach for the treatment of hepatoma ascites and other malignant effusions [ 151 ].…”