Cui Jiarong, Dong Jia, Lang Yutong, Liu Xiaoyang, Qi Yuchen, Zheng Yixin, Wang Ruoxi, Hu Huiqun, Zhou Min
Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
ACS Nano. 2025 Aug 5;19(30):27634-27653. doi: 10.1021/acsnano.5c07135. Epub 2025 Jul 22.
Radiodermatitis, one of the most prevalent side effects of cancer radiotherapy, is characterized by cellular oxidative stress, mitochondrial damage, and inflammatory responses. In this study, we isolated extracellular vesicles (EVs) from the natural microalgae (SP) and engineered them by loading astaxanthin (AST) into SP-EVs, resulting in the formation of SP-EVs@AST. This engineered system significantly enhanced the solubility and stability of AST while preserving the structural integrity and biological activity of SP-EVs, thereby enabling the complementary and synergistic effects of AST and SP-EVs. SP-EVs@AST demonstrated protective effects against radiation-induced cellular damage by alleviating oxidative stress, restoring mitochondrial function, and reducing inflammatory responses. To optimize topical administration, SP-EVs@AST were incorporated into a self-assembled hydrogel composed of aldehyde-functionalized hyaluronic acid (HA-CHO) and carboxymethyl chitosan (CMCS), forming a skin radiation protection dressing (SP-EVs@AST gel). This dressing effectively preserved the activity of SP-EVs@AST, facilitated its sustained release, protected the skin from progressive radiation-induced injury, and exhibited long-term biological safety. This system demonstrates the potential of engineered microalgal EVs as carriers for poorly soluble drugs, offering a promising strategy to expand their application as a targeted drug delivery platform in biomedical fields.
放射性皮炎是癌症放射治疗最常见的副作用之一，其特征为细胞氧化应激、线粒体损伤和炎症反应。在本研究中，我们从天然微藻（SP）中分离出细胞外囊泡（EVs），并通过将虾青素（AST）载入SP-EVs对其进行改造，从而形成了SP-EVs@AST。这种工程化系统显著提高了AST的溶解度和稳定性，同时保留了SP-EVs的结构完整性和生物活性，从而实现了AST与SP-EVs的互补和协同作用。SP-EVs@AST通过减轻氧化应激、恢复线粒体功能和减少炎症反应，对辐射诱导的细胞损伤表现出保护作用。为了优化局部给药，将SP-EVs@AST掺入由醛基功能化透明质酸（HA-CHO）和羧甲基壳聚糖（CMCS）组成的自组装水凝胶中，形成皮肤辐射防护敷料（SP-EVs@AST凝胶）。该敷料有效保留了SP-EVs@AST的活性，促进其持续释放，保护皮肤免受渐进性辐射诱导损伤，并表现出长期生物安全性。该系统证明了工程化微藻EVs作为难溶性药物载体的潜力，为其在生物医学领域作为靶向药物递送平台的应用拓展提供了一种有前景的策略。
