Biomimetic Nanoparticles With Overexpressed Adhesion Proteins for Targeted Delivery of Gambogic Acid in Hepatocellular Carcinoma

Cancer cell membrane coating offers a promising strategy for targeted drug delivery, yet its homotypic targeting mechanism and optimization remain insufficiently understood. This study identifies epithelial cell adhesion molecule (EpCAM), rather than Galectin-3, as the pivotal mediator of homologous uptake in hepatocellular carcinoma. Through genetic engineering, HepG2 cells overexpressing EpCAM are generated, and their membranes are used to coat gambogic acid-loaded PLGA nanoparticles. Cellular uptake assays reveal that EpCAM-enriched membranes significantly enhance nanoparticle internalization by homologous cancer cells via clathrin-mediated endocytosis, a process dependent on both clathrin heavy chain and light chain. In vivo biodistribution studies demonstrate that the EpCAM-engineered biomimetic platform markedly improves tumoral drug accumulation and retention, leading to potent antitumor efficacy through BAX/BCL-2-mediated apoptosis without inducing significant systemic toxicity. Mechanistically, this enhanced targeting is attributed to multivalent EpCAM-EpCAM interactions and the preservation of native membrane functionalities, including immune evasion and prolonged circulation. By elucidating the molecular machinery driving membrane-mediated homotypic recognition, this work establishes a rational basis for engineering cell membranes with overexpressed adhesion proteins, thereby enabling a novel and translatable strategy for precision chemotherapy delivery in hepatocellular carcinoma and potentially other epithelial tumors.

Abstract from PubMed (PMID 42934174). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.