Microchip Based Isolation and Drug Delivery of Patient-Derived Extracellular Vesicles Against Their Homologous Tumor.

Abstract

Extracellular vesicles (EVs) have demonstrated significant potential in drug delivery and anti-tumor therapy. Despite this promising strategy, challenges such as specific targeting, EVs purification persist. In this study, a personalized nanodrug delivery platform using patient-derived tumor EVs (PT-EVs) based on a microchip is presented. The microchip integrates multiple functions, including capture, enrichment, drug loading, and elution of PT-EVs. The isolation and drug-carrying procedures are completed within a 12 h timeframe, achieving a recovery rate of 65%, significantly surpassing the conventional ultracentrifuge (UC) method. Furthermore, PT-EVs derived from patient tumor models are first utilized as natural drug carriers, capitalizing on their inherent homing ability to precisely target homologous tumors. Lenvatinib and doxorubicin (DOX), two commonly utilized drugs in the clinical treatment of hepatocellular carcinoma (HCC), are loaded into PT-EVs and delivered to a matched in vitro tumor model that recapitulates original tumors for drug susceptibility testing. As is proven, PT-EVs exhibit robust tumor cell targeting and efficient receptor-mediated cellular uptake, and the efficacy of chemotherapeutic drugs is improved significantly. These results suggest that this platform could be a valuable tool for efficient isolation of PT-EVs and personalized drug customization, particularly when working with limited clinical samples, thus supporting personalized and precision medicine.