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Lysosome-instructed Self-assembly of Amino Acid-functionalized Perylenediimide for the Multidrug-resistant Cancer Treatment

초록/요약

Multidrug resistance (MDR) of cancer cells reduces chemotherapeutic efficacy by preventing drug accumulation through drug efflux pump and lysosomal sequestration/exocytosis. Herein, lysosome-targeting organelle-localization-induced supramolecular self-assembly (OLISA) of perylene diimide (PDI) derivatives is presented as a powerful strategy to overcome anticancer resistance. Stimulated by the lysosomal low pH, the amphiphilic PDI derivatives functionalized with amino acids (PDI-AAs) construct fibrous self-assembly inside the lysosomes, causing cancer cell apoptosis by lysosomal rupture with negligible apoptosis for normal cell. The agglomerated assemblies were not removed by lysosomal exocytosis, thereby displaying a 10.7-fold higher anticancer efficacy on MDR cancer compared to a doxorubicin chemotherapeutic agent. The MDR-circumventing capability support PDI-AAs as potential candidates for the treatment of MDR cancer cells by lysosome-targeting OLISA.

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