Self-Assembled Nanoparticles from Cationic Dipeptides and D-π-A Chromophores for Near-Infrared Photothermal Therapy

Developing nanoformulations that combine potent photothermal efficacy with robust biocompatibility remains a critical hurdle for precision cancer therapy. Herein, we successfully fabricated CDPNCs-Z3 composite nanoparticles featuring a distinctive spiky architecture via an induced reconstruction self-assembly strategy using cationic dipeptides (CDP). In contrast to simple physical encapsulation, the incorporation of the functional guest molecule Z3 drives the synergistic reconstruction of CDP from fibrous aggregates into smaller, monodisperse particulate nanostructures. This distinct morphological transformation is ascribed to the combined effects of π-π stacking between Z3 and the CDP aromatic system and the presence of strong electron-withdrawing groups. Under 808 nm laser irradiation, these composite nanoparticles demonstrate superior photothermal performance and exceptional cycling stability. In vitro assays further validated their high cellular penetration, negligible dark toxicity, and potent photothermal killing effect. This work not only establishes a versatile new paradigm for building peptide-based nanostructures but also lays a solid foundation for designing safe and effective next-generation photothermal therapeutic agents.