Ren Xiaohong, Wang Siwen, Teng Yupu, Zheng Shiyu, Li Feng, Wang Caifen, Wu Li, Zhang Jiwen
School of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Carbohydr Polym. 2025 Mar 15;352:123160. doi: 10.1016/j.carbpol.2024.123160. Epub 2024 Dec 18.
Extracellular vesicles (EVs) are promising therapeutic carriers for their ideal nano-size and intrinsic biocompatibility, while rapid clearance and limited targeting ability are the major setbacks of EVs. With minimal absorption into the systemic circulation, inhalation for pulmonary disease therapy minimizes off-target toxicity to other organs and offers a safe and effective treatment for respiratory disorders. Herein, a nano-grid carrier made of boronated cyclodextrin framework (BCF) was prepared for pH/HO responsive release of EVs. A novel design of cyclo (Arg-Gly-Asp-D-Tyr-Lys) peptide (RGD)-modified milk-derived EVs (mEVs) loaded in the BCF particles (RGD-mEVs@BCF) was developed for pulmonary delivery. The results indicated that RGD-mEVs showed superior anti-inflammatory activity in contrast with mEVs in vitro. BCF was able to capture and protect RGD-mEVs, which showed extended-release profiles and responsiveness. Pulmonary administration of RGD-mEVs@BCF showed favorable biocompatibility in rats. Taken together, RGD-mEVs@BCF features biocompatibility and pH-responsive mEVs release as a therapeutic platform for pulmonary delivery of drugs to treat lung diseases, especially for inflammatory diseases.
细胞外囊泡（EVs）因其理想的纳米尺寸和固有的生物相容性而有望成为治疗载体，然而，快速清除和有限的靶向能力是EVs的主要障碍。通过最小化进入体循环的吸收，吸入用于肺部疾病治疗可将对其他器官的脱靶毒性降至最低，并为呼吸系统疾病提供安全有效的治疗。在此，制备了一种由硼化环糊精框架（BCF）制成的纳米网格载体，用于EVs的pH/HO响应释放。开发了一种新型设计的环（精氨酸-甘氨酸-天冬氨酸-D-酪氨酸-赖氨酸）肽（RGD）修饰的负载在BCF颗粒中的乳源EVs（mEVs）（RGD-mEVs@BCF）用于肺部递送。结果表明，与体外的mEVs相比，RGD-mEVs表现出优异的抗炎活性。BCF能够捕获和保护RGD-mEVs，其显示出缓释特性和响应性。RGD-mEVs@BCF的肺部给药在大鼠中显示出良好的生物相容性。综上所述，RGD-mEVs@BCF具有生物相容性和pH响应性mEVs释放特性，可作为治疗肺部疾病，尤其是炎症性疾病的肺部药物递送治疗平台。
