https://scholars.lib.ntu.edu.tw/handle/123456789/637223
標題: | Lysosomal-targeted doxorubicin delivery using RBC-derived vesicles to overcome drug-resistant cancer through mitochondrial-dependent cell death | 作者: | CHIH-PENG LIN Wu, Shu-Hui Lin, Tzu-Yin Chu, Chia-Hui Lo, Leu-Wei Kuo, Ching-Chuan Chang, Jang-Yang SZU-CHUN HSU BOR-SHENG KO MING YAO Hsiao, Jong-Kai Wang, Shih-Wei Huang, Dong-Ming |
關鍵字: | Cancer chemotherapy; Doxorubicin; Drug delivery; Multidrug resistance; Nanoparticle; RBC | 公開日期: | 4-十月-2023 | 卷: | 197 | 來源出版物: | Pharmacological research | 摘要: | Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637223 | ISSN: | 10436618 | DOI: | 10.1016/j.phrs.2023.106945 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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