Lysosome-Instructed Self-Assembly of Amino-Acid-Functionalized Perylene Diimide for Multidrug-Resistant Cancer Cells.

Abstract

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 lysosome-targeted self-assembly.

• Authors: Changjoon Keum, Jiyoung Hong, Doyeon Kim, Sang-Yup Lee, Hyuncheol Kim
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 13 Issue 13 Pg. 14866-14874 (Apr 07 2021) ISSN: 1944-8252 [Electronic] United States
• PMID: 33759486 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Antineoplastic Agents
• Imides
• perylenediimide
• Perylene

Topics

• Amino Acids (chemistry, pharmacology)
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Imides (chemistry, pharmacology)
• Lysosomes (drug effects, metabolism)
• Neoplasms (drug therapy, metabolism)
• Perylene (analogs & derivatives, chemistry, pharmacology)