Lysosome-Instructed Self-Assembly of Amino-Acid-Functionalized Perylene Diimide for Multidrug-Resistant Cancer Cells
- 주제(키워드) 도움말 lysosome , cancer , self-assembly , perylene diimide , multidrug resistance
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2021
- 총서유형 Journal
- 본문언어 영어
초록/요약 도움말
Multidrug resistance (MDR) of cancer cells reduces chemotherapeutic efficacy by preventing drug accumulation in the cells through a drug efflux pump and lysosomal sequestration/exocytosis. Herein, to overcome such anticancer resistance, lysosome-targeted self-assembly of perylene diimide (PDI) derivatives is presented as a powerful strategy for effective and selective anticancer therapy. Stimulated by the lysosomal low pH, the amphiphilic PDI derivatives functionalized with amino acids (PDI-AAs) construct fibrous self-assembled structures inside the lysosomes, causing cancer cell apoptosis by lysosomal rupture. In contrast, negligible apoptosis was observed from normal cells by PDI-AA. The agglomerated fibrous assemblies were not removed by lysosomal exocytosis, thereby displaying a 10.7-fold higher anticancer efficacy on MDR cancer cells compared to a doxorubicin chemotherapeutic agent. The MDR-circumventing capability, along with high selectivity toward cancer cells, supports PDI-AAs as potential candidates for the treatment of MDR cancer cells by lysosometargeted self-assembly.
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