Extracellular Vesicles as Nanoparticle Delivery Vectors in Cancer Therapy.

Abstract

Three decades after the approval of the first cancer nanomedicine, low (<1%) tumor delivery remains the central unsolved challenge in nanoparticle (NP)-based therapy. This barrier has prompted a research shift toward biologically derived delivery systems able to reduce immune clearance while preserving tumor-homing capabilities. In particular, extracellular vesicles (EVs) seem obvious candidates on account of their intrinsic biocompatibility, cell-specific tropism, and biological functionality. In this mini-review, we critically analyze EVs as nanoparticle delivery vectors in cancer therapy. We describe current EV engineering approaches, including loading methodologies, surface modification strategies, and the development of artificial or biomimetic EVs, highlighting technical, scalability, and characterization challenges. We also summarize key <i>in vitro</i> and <i>in vivo</i> results, addressing encapsulation strategy, biodistribution, and therapeutic outcomes. From this discussion, we outline research needs that must be addressed to develop EV-NP hybrids as tools to overcome the delivery challenge in cancer.