Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi Hiroshima, 739-8527, Japan.
Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
J Mater Chem B. 2024 Oct 2;12(38):9760-9766. doi: 10.1039/d4tb00416g.
Extracellular vesicles (EVs) have excellent biocompatibility and long retention times in the circulation and have consequently been expected to be useful as drug-delivery systems. However, their applications have been limited because of the inability to introduce hydrophobic compounds to EVs without the use of harmful organic solvents. Herein, we developed an organic-solvent-free drug-loading technique based on the host exchange reaction. We demonstrated that the exchange reaction enabled quantitative loading of EVs with highly concentrated (0.1 mM) hydrophobic fullerene derivatives. Fullerene derivative-loaded EVs (EVs/C) could eliminate cancer cell lines more efficiently than fullerene derivative-loaded liposomes (Lip/C). Moreover, the photodynamic activity of EVs/C was fivefold higher than that of the clinically available photosensitizer photofrin. EVs/C could efficiently suppress tumor growth in tumor-xenograft model mice.
细胞外囊泡 (EVs) 具有极好的生物相容性和在循环系统中的长时间保留时间，因此有望作为药物递送系统。然而，由于不能在不使用有害有机溶剂的情况下向 EVs 中引入疏水性化合物，因此它们的应用受到限制。在此，我们开发了一种基于主客体交换反应的无有机溶剂药物加载技术。我们证明，交换反应能够定量地将高浓度（0.1mM）疏水性富勒烯衍生物加载到 EVs 中。与负载富勒烯衍生物的脂质体（Lip/C）相比，负载富勒烯衍生物的 EVs（EVs/C）能够更有效地消除癌细胞系。此外，EVs/C 的光动力活性是临床可用光敏剂血卟啉的五倍。EVs/C 能够有效地抑制肿瘤异种移植模型小鼠的肿瘤生长。
