3P Biotechnologies, Inc., Louisville, KY, 40202, USA.
Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Cancer Lett. 2023 May 1;561:216141. doi: 10.1016/j.canlet.2023.216141. Epub 2023 Mar 22.
Chemotherapeutics continue to play a central role in the treatment of a wide variety of cancers. Conventional chemotherapy involving bolus intravenous doses results in severe side effects - in some cases life threatening - delayed toxicity and compromised quality-of-life. Attempts to deliver small drug molecules using liposomes, polymeric nanoparticles, micelles, lipid nanoparticles, etc. have produced limited nanoformulations for clinical use, presumably due to a lack of biocompatibility of the material, costs, toxicity, scalability, and/or lack of effective administration. Naturally occurring small extracellular vesicles, or exosomes, may offer a solution and a viable system for delivering cancer therapeutics. Combined with their inherent trafficking ability and versatility of cargo capacity, exosomes can be engineered to specifically target cancerous cells, thereby minimizing off-target effects, and increasing the efficacy of cancer therapeutics. Exosomal formulations have mitigated the toxic effects of several drugs in murine cancer models. In this article, we review studies related to exosomal delivery of both small molecules and biologics, including siRNA to inhibit specific gene expression, in the pursuit of effective cancer therapeutics. We focus primarily on bovine milk and colostrum exosomes as the cancer therapeutic delivery vehicles based on their high abundance, cost effectiveness, scalability, high drug loading, functionalization of exosomes for targeted delivery, and lack of toxicity. While bovine milk exosomes may provide a new platform for drug delivery, extensive comparison to other nanoformulations and evaluation of long-term toxicity will be required to fully realize its potential.
化疗在治疗各种癌症中继续发挥核心作用。传统的化疗涉及静脉推注大剂量药物,会导致严重的副作用——在某些情况下甚至危及生命——延迟毒性和降低生活质量。尝试使用脂质体、聚合物纳米颗粒、胶束、脂质纳米颗粒等方法递送小分子药物,仅产生了有限的可用于临床的纳米制剂,这可能是由于材料的生物相容性、成本、毒性、可扩展性和/或缺乏有效给药方式的原因。天然存在的小细胞外囊泡或外泌体可能提供一种解决方案,是一种有前途的递送癌症治疗剂的系统。外泌体结合其固有的运输能力和货物载量的多功能性,可以被设计成专门靶向癌细胞,从而最大限度地减少脱靶效应,并提高癌症治疗剂的疗效。外泌体制剂减轻了几种药物在小鼠癌症模型中的毒性作用。在本文中,我们综述了与外泌体递送小分子和生物制剂相关的研究,包括 siRNA 以抑制特定基因表达,以寻求有效的癌症治疗剂。我们主要关注牛初乳和牛初乳外泌体作为癌症治疗药物的递送载体,因为它们的丰度高、成本效益高、可扩展性高、药物载量高、可对外泌体进行功能化以实现靶向递送,且毒性低。虽然牛初乳外泌体可能为药物递送提供了一个新平台,但仍需要与其他纳米制剂进行广泛比较,并评估其长期毒性,以充分发挥其潜力。
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