Exosome-mimetic nanoplatforms for targeted cancer drug delivery

作者：Abi Judit Vázquez-Ríos, Ángela Molina-Crespo, Belén L. Bouzo, Rafael López‐López, Gema Moreno‐Bueno, María de la Fuente · 发表于：Journal of Nanobiotechnology · 年份：2019 · DOI：10.1186/s12951-019-0517-8 · 被引用次数：180 · 研究领域：Extracellular vesicles in disease、Nanoparticle-Based Drug Delivery、RNA Interference and Gene Delivery

BACKGROUND: Lack of effective tumor-specific delivery systems remains an unmet clinical challenge for successful translation of innovative therapies, such as, therapeutic oligonucleotides. In the past decade, exosomes have been suggested to be ideal drug delivery systems with application in a broad range of pathologies including cancer, due to their organotropic properties. Tumor-derived exosomes, having tumor-homing properties, can efficiently reach cancer cells and therefore behave as carriers for improved drug delivery to the primary tumor and metastases. However, due to their complex composition, and still undefined biological functions, safety concerns arise hampering their translation to the clinics. RESULTS: We propose here the development of exosome-mimetic nanosystems (EMNs) that simulate natural tumor-derived exosomes with respect to their structure and functionality, but with a controlled composition, for the targeted delivery of therapeutic oligonucleotides to lung adenocarcinoma cells (microRNA-145 mimics). Making use of the well-known liposome technology, EMNs can be engineered, loaded with the therapeutic compounds, and tailored with specific proteins (integrin α6β4) providing them organotropic properties. EMNs show great similarities to natural exosomes with respect to their physicochemical properties, drug loading capacity, and ability to interact with the cancer target cells in vitro and in vivo, but are easier to manufacture, can be produced at high yields,...