化疗药物的不精确靶向通常会导致乳腺癌治疗过程中的严重毒性。为了解决这个问题，我们设计了一种策略，将达卡巴嗪（DC）加载到基于岩藻糖的碳量子点（CQD）中，随后涂上来自乳腺癌细胞的外泌体（Ex-DC@CQD）。纳米颗粒追踪分析和蛋白质印迹显示Ex-DC@CQD保留了外泌体的结构和功能特征。我们发现外泌体通过硫酸乙酰肝素蛋白聚糖（HSPG）受体促进DC@CQD转运至癌细胞，随后增强线粒体膜电位的去极化、ROS的产生以及诱导细胞凋亡，从而导致细胞死亡。体内成像和药代动力学研究表明，与游离 DC 相比，其抗肿瘤靶向性和功效增强，我们将其归因于药代动力学特征的改善、通过外泌体介导的 HSPG 受体驱动的细胞摄取实现更大的肿瘤积累以及 Ex-DC@ 的持续释放CQD。我们的研究结果可能为进一步开发用于乳腺癌靶向的生物来源纳米载体铺平道路。版权所有 © 2023。由 Elsevier B.V. 出版。

Imprecise targeting of chemotherapeutic drugs often leads to severe toxicity during breast cancer therapy. To address this issue, we have devised a strategy to load dacarbazine (DC) into fucose-based carbon quantum dots (CQDs), which are subsequently coated with exosomes (Ex-DC@CQDs) derived from breast cancer cells. Nanoparticle tracking analysis and western blotting revealed that Ex-DC@CQDs retained the structural and functional characteristics of exosomes. We found that exosomes facilitated the transport of DC@CQDs to cancer cells via heparan sulfate proteoglycan (HSPG) receptors, followed by an augmented depolarization of the mitochondrial membrane potential, ROS generation, and induction of apoptosis leading to cell death. In vivo imaging and pharmacokinetic studies demonstrated enhanced antitumor targeting and efficacy compared to free DC which we attribute to an improved pharmacokinetic profile, a greater tumor accumulation via exosome-mediated- HSPG receptor-driven cell uptake, and sustained release of the Ex-DC@CQDs. Our findings may pave the way for the further development of biologically sourced nanocarriers for breast cancer targeting.Copyright © 2023. Published by Elsevier B.V.