School of Medicine, and Centre for Molecular and Medical Research, Deakin University, Waurn Ponds, Australia.
School of Medicine, and Centre for Molecular and Medical Research, Deakin University, Waurn Ponds, Australia; School of Nursing, Zhengzhou University, Zhengzhou 450001, PR China.
Int J Pharm. 2019 Jul 20;566:697-707. doi: 10.1016/j.ijpharm.2019.06.028. Epub 2019 Jun 15.
Despite their great potential, the nano-sized extracellular vesicles are yet to become effective delivery systems for poorly water-soluble drugs. Here, we present a novel platform of exosomes as a drug delivery system by engineering of a poorly water-soluble drug into a poloxamer-based molecular nanostructured dispersion composed of a hydrophilic and a hydrophobic moiety for an enhanced anticancer efficacy. For the first time, aspirin was loaded into exosomes as an anticancer agent via a one-step fabrication combining the nano-matrix formation of the nanostructured dispersion and exosomes loading. Our approach could transform crystalline aspirin to a nanoamorphous form in the nano-matrix structured exosomes, leading to increased drug encapsulation efficiency for exosomes, improved dissolution and strongly enhanced cytotoxicity of aspirin to cancer cells. Interestingly, cytotoxicity of aspirin to both breast and colorectal cancer cells could be strongly enhanced by the nanoamorphous aspirin-loaded exosomes, and this cytotoxic effect was more pronounced to parental cells of the exosomes, reminiscent of homing effect. Hence, this study has pioneered a novel nanoplatform of nanoamorphous exosomal delivery system to transform an anti-inflammatory drug into a potent anti-cancer agent.
尽管具有巨大的潜力，但纳米尺寸的细胞外囊泡尚未成为水溶性差的药物的有效递送系统。在这里，我们通过将一种水溶性差的药物工程化为由亲水性和疏水性部分组成的基于泊洛沙姆的分子纳米结构分散体，构建了一种新型的外泌体作为药物递送系统，以增强抗癌效果。首次通过将纳米结构分散体的纳米基质形成与外泌体加载相结合的一步法制备，将阿司匹林负载到外泌体中作为抗癌剂。我们的方法可以使结晶阿司匹林在纳米基质结构的外泌体中转化为纳米无定形形式，从而提高外泌体的药物包封效率，改善阿司匹林的溶解性能，并强烈增强其对癌细胞的细胞毒性。有趣的是，纳米无定形阿司匹林负载的外泌体可强烈增强阿司匹林对乳腺癌和结直肠癌细胞的细胞毒性，并且这种细胞毒性作用对外泌体的亲本细胞更为明显，类似于归巢效应。因此，本研究开创了一种新型的纳米无定形外泌体递送系统纳米平台，将抗炎药物转化为有效的抗癌药物。
