Nano-biohybrid systems for the targeted delivery of chemotherapeutics

Extracellular vesicles, as a form of cell-derived drug delivery systems (DDSs), have emerged as a novel alternative to their synthetic counterparts (<i>e.g.</i> liposomes) due to advantages associated with their intrinsic biocompatibility, non-immunogenicity and tissue-targeting ability. Nonetheless, the clinical application of these naturally secreted vesicles is still hindered by tedious isolation methods, poor drug-loading efficiencies and difficulties in surface functionalization. Our group has conceived a biohybrid DDS, termed nano-cell vesicle technology systems (nCVTs), through the fusion of cellular membranes and synthetic lipids. nCVTs are expected to combine the benefits of both the synthetic lipids and the cellular component. Here, we report the production of doxorubicin (DOX)-loaded nCVTs <i>via</i> thin-film rehydration and extrusion, showing high loading efficiency, intrinsic targeting abilities, preferential uptake in cancer cells and a superior <i>in vivo</i> anticancer effect compared with DOX-loaded liposomes and the free drug. With the administration of DOX-loaded nCVTs, we observed an improvement in tumor growth inhibition without any significant cardiac toxicity detected. Taken together, our results suggest the potential of nCVTs to be developed as a promising DDS for the targeted delivery of chemotherapeutics.