College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China.
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China; Research Institute of Shenzhen, Wuhan University, Shenzhen, 518057, PR China.
Biomaterials. 2021 Dec;279:121234. doi: 10.1016/j.biomaterials.2021.121234. Epub 2021 Oct 28.
Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.
细胞外囊泡 (EVs) 由于其出色的生物相容性和长期循环，已成为多功能药物递送载体，但由于其固有的低靶向性和低效的载药能力，限制了其应用。在此，我们报告了一种简单可行的原位生物合成方法，用于包裹具有细胞内产生的原卟啉 X (PpIX) 和阿霉素 (DOX) 的肿瘤靶向叶酸 (FA) 修饰的 EVs。与传统的直接药物孵育或药物电穿孔 EVs 相比，这些生物合成的 EVs 显示出更高的载药效率，同时最小化了结构和功能的干扰。我们的多功能 EVs 显示出增强的积累和渗透到深部肿瘤实质，以及增强的免疫反应来消融原位和转移性肿瘤，从而实现更可靠的光化疗。作为一种智能多模式治疗系统，我们的生物合成 EVs 可以与更多的治疗剂结合，并为生物医学应用提供了巨大的潜力。
