Targeting capacity, safety and efficacy of engineered extracellular vesicles delivered by transdermal microneedles to treat plasmacytoma in mice

作者：Yulin Cao, Xuan Hu, Di Wu, Yuxuan Jiang, Yali Yu, Shan Wang, Wenlan Chen, Yaoying Long, Liuyue Xu, Jiao Qu, Bianlei Yang, Blal Chakhabi, Hongxiang Wang, Yong Deng, Lei Chen, Zhichao Chen, Qiubai Li · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70327 · 被引用次数：7 · 研究领域：Extracellular vesicles in disease、Advancements in Transdermal Drug Delivery、Cutaneous lymphoproliferative disorders research

Abstract Background Engineered extracellular vesicles (EVs) are emerging as a highly potential platform for targeted drug delivery in cancer therapy. Although intravenous injection is commonly used in EV treatment, there is growing interest in using microneedles (MNs) for transdermal EV delivery; however, comprehensive studies comparing the tissue distribution, safety and antitumour efficacy of these two approaches for delivering engineered EVs remain scarce. Methods We used EVs derived from umbilical cord mesenchymal stem cells, modified with phospholipid‒polyethylene glycol‒N‐hydroxysuccinimide and conjugated with CD38 peptides (CD38‐EVs), to target myeloma cells that highly express CD38 antigen, and tested their safety and antitumour efficacy in mice with subcutaneous plasmacytoma, administrated via dissolvable transdermal MNs or intravenous injection. Flow cytometry, immunofluorescence and fluorescence molecular projection imaging analysis were employed to evaluate the distribution of CD38‐EVs at the cellular level and within living systems. Additionally, histopathological analysis and biochemical analyses were conducted to assess the antitumour effects and safety of CD38‐EVs loaded with doxorubicin (CD38‐EVs‐Dox). Results Compared to standard EVs, CD38‐EVs exhibited enhanced uptake by CD38 high tumour cells and reduced uptake by CD38‐negative non‐tumour cells in vitro. In plasmacytoma NOD/SCID mouse models, CD38‐EVs encapsulated within MNs (CD38‐EVs MNs ) effectively tar...