Engineered extracellular vesicles loaded in boronated cyclodextrin framework for pulmonary delivery

IF 12.5 1区化学 Q1 CHEMISTRY, APPLIED Carbohydrate Polymers Pub Date : 2025-03-15 Epub Date: 2024-12-18 DOI:10.1016/j.carbpol.2024.123160

Xiaohong Ren , Siwen Wang , Yupu Teng , Shiyu Zheng , Feng Li , Caifen Wang , Li Wu , Jiwen Zhang

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Abstract

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/H₂O₂ 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.

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工程细胞外囊泡装载在硼化环糊精框架肺输送。

细胞外囊泡（Extracellular vesicles, EVs）因其理想的纳米尺寸和内在的生物相容性而成为很有前景的治疗载体，但快速清除和有限的靶向能力是EVs的主要缺点。吸入治疗肺部疾病的体循环吸收最小，最大限度地减少了对其他器官的脱靶毒性，并为呼吸系统疾病提供了安全有效的治疗方法。本文制备了硼化环糊精框架（BCF）纳米栅格载体，用于电动汽车的pH/H2O2响应释放。设计了一种新型的环（Arg-Gly-Asp-D-Tyr-Lys）肽（RGD）修饰的牛奶衍生ev (mev)，装载在BCF颗粒中（RGD-mEVs@BCF），用于肺输送。结果表明，rgd - mev体外抗炎活性优于mev。BCF能够捕获和保护rgd - mev， rgd - mev表现出延长释放的特征和响应性。肺部给药RGD-mEVs@BCF在大鼠体内具有良好的生物相容性。综上所述，RGD-mEVs@BCF具有生物相容性和ph响应性mev释放的特点，可作为肺部药物递送的治疗平台，用于治疗肺部疾病，特别是炎症性疾病。

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来源期刊

Carbohydrate Polymers 化学-高分子科学

CiteScore

22.40

自引率

8.00%

发文量

1286

审稿时长

47 days

期刊介绍： Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience. The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.