Pourali Parastoo, Neuhöferová Eva, Yahyaei Behrooz, Svoboda Milan, Buchnarová Adéla, Benson Veronika
Department of Chemistry, University of Wyoming, 1000 E. University Ave., Laramie, WY 82071, USA.
Institute of Microbiology, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Pharmaceutics. 2025 Aug 5;17(8):1015. doi: 10.3390/pharmaceutics17081015.
Extracellular vesicles (EVs) are involved in cell-to-cell communication and delivery of signaling molecules and represent an interesting approach in targeted therapy. This project focused on EV-mediated facilitation and cell-specific delivery of effector antimiR molecules carried by biologically produced gold nanoparticles (AuNPs). First, we loaded EVs derived from cancer cells 4T1 with AuNPs-antimiR. The AuNPs were also decorated with or without transferrin (Tf) molecules. We examined parental cell-specific delivery of the AuNPs-Tf-antimiR within monocultures as well as co-cultures in vitro. Subsequently, we used autologous EVs containing AuNPs-Tf-antimiR to target tumor cells in a xenograft tumor model in vivo. Efficacy of the antimir transfer was assessed by qPCR and apoptosis assessment. In vitro, EVs loaded with AuNPs-antimiR were internalized only by the parental cells and the AuNPs-antimiR transfer was successful and effective only in EVs that were decorated with Tf. We achieved effective delivery of the antimiR molecule into cancer cells in vivo, which was proved by specific silencing of the target oncogenic miRNA as well as induction of cancer cells apoptosis. EVs represent an interesting and potent way for targeted cargo delivery and personalized medicine. On the other hand, there are various safety and efficacy challenges that remain to be addressed.
细胞外囊泡（EVs）参与细胞间通讯和信号分子传递，是靶向治疗中一种引人关注的途径。本项目聚焦于由生物合成的金纳米颗粒（AuNPs）携带的效应抗miR分子的EV介导促进作用和细胞特异性递送。首先，我们用AuNPs - antimiR装载源自癌细胞4T1的EVs。AuNPs还用转铁蛋白（Tf）分子进行了修饰或未修饰。我们在体外单一培养物以及共培养物中研究了AuNPs - Tf - antimiR的亲代细胞特异性递送。随后，我们在体内异种移植肿瘤模型中使用含有AuNPs - Tf - antimiR的自体EVs靶向肿瘤细胞。通过qPCR和凋亡评估来评估抗miR转移的效果。在体外，装载有AuNPs - antimiR的EVs仅被亲代细胞内化，并且AuNPs - antimiR转移仅在用Tf修饰的EVs中成功且有效。我们在体内实现了抗miR分子向癌细胞的有效递送，这通过靶致癌miRNA的特异性沉默以及癌细胞凋亡的诱导得到证明。EVs是靶向货物递送和个性化医学中一种有趣且有效的方式。另一方面，仍有各种安全性和有效性挑战有待解决。
