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 lysosometargeted self-assembly.

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

“…This basic investigation of supramolecular self-assembly was done because we had found a relationship between cytotoxicity and ability of compounds to form supramolecular aggregates capable of affecting cytotoxicity [ 10 , 35 ]. Similar results have recently been published by other authors [ 40 , 41 ]. More detailed information is presented in Table S1 (Supplementary Material) .…”

Triterpenoid–PEG Ribbons Targeting Selectivity in Pharmacological Effects

“…The target compounds were tested to show their ability to form supramolecular gels. This investigation was made because we have found a relationship between cytotoxicity and the ability of compounds to form supramolecular aggregates capable of affecting cytotoxicity [43,47], and similar results have recently been published by other authors [48,49]. Among the studied series of compounds, the only 4c, 6c, and 6d produced a gel in glycerol; 8a produced a gel in ethylene glycol (Supplementary material, Figure S1).…”

Photosensitive Chitosan-Based Injectable Hydrogel Chemically Cross-Linked by Perylene Bisimide Dopamine with Robust Antioxidant and Cytotoxicity Enhancer Properties for In Vitro Photodynamic Therapy of Breast Cancer

“…Perylene diimide (PDI) derivatives exhibited tremendous potential as a PS in PDT applications due to their excellent thermal and photostability, high extinction coefficients, low dark toxicity, and significant singlet oxygen quantum yield. , Structurally, PDI is a rigid hydrophobic aromatic polycyclic molecule, and its π–π aggregation has limited its biological application. , Interestingly, by conjugating PDIs with biological molecules such as amino acids and short peptide sequences, soluble structures are created with unique optical, physicochemical, and structural properties, which could modulate the self-assembly of PDI for different biomedical applications. − Several groups have reported using conjugated PDI derivatives due to their stability, phototoxicity, and biocompatibility properties in PDT …”