Self-assembly of tripeptides and anticancer drug into nanostructures via synergistic non-covalent interactions for enhanced photodynamic therapy

Among anticancer modalities, photodynamic therapy (PDT) using self-assembled nanomaterials has emerged as a promising non-invasive approach for cancer treatment. However, poor stability, biocompatibility, and a lack of structure-function relationship are real challenges and self-assembled peptide nanoformulations offer an effective strategy to overcome these limitations. In this study, we report the development of peptides-modulated self-assembled nanoparticles of anticancer drug chlorin e6 (Ce-6) and two tripeptides (Ac-IFH-NH 2 , NH 2 -IFH-COOH) through synergistic effects of non-covalent interactions. The tripeptides act as structural modulators; molecular simulations reveal that electrostatic interactions and π–π stacking are key factors in governing the assembly process. The resulting nanostructures display H-type aggregation, confirming strong interactions between the tripeptides and drug molecules. Compared with free Ce-6, the self-assembled nanoparticles exhibit significantly enhanced photodynamic activity upon light activation, enabling selective cancer cell death. This self-assembly strategy provides a practical and versatile platform to enhance anticancer efficacy and paves the way for developing advanced therapeutics for targeted cancer therapy.