pH-responsive chiral supramolecular cysteine-Zn2+-indocyanine green assemblies for triple-level chirality-specific anti-tumor efficacy

Chirality, ubiquitous in living matter, plays vital roles in a series of physiological processes. The clarification of the multiple functions of chirality in bioapplications may provide innovative methodologies for engineering anti-tumor agents. Nevertheless, the related research has been rarely explored. In this study, the chiral supramolecular l/d-cysteine (Cys)-Zn2+-indocyanine green (ICG) nanoparticles were constructed through the coordination interaction between l/d-Cys and Zn2+, followed by the encapsulation of ICG. Experimental findings revealed that the l/d-Cys-Cys-Zn2+-ICG exhibited 17.31 times higher binding affinity toward phospholipid-composed liposomes compared to l-Cys-Zn2+-ICG. Furthermore, driven by chirality-specific interaction, a 2.07 folds greater cellular internalization of d-Cys-Zn2+-ICG than l-Cys-Zn2+-ICG was demonstrated. Additionally, the triple-level chirality-dependent photothermal, photodynamic and Zn2+ releasing anti-tumor effects of l/d Cys-Zn2+-ICG in vitro were verified. As a result, the d-formed nanoparticles achieved 1.93 times higher anti-tumor efficiency than the l-formed ones. The triple-level chirality-mediated anti-tumor effect highlighted in this study underscores the enormous potential of chirality in biomedicine and holds substantial significance in improving cancer therapeutic efficacy. In this study, chiral supramolecular l/d-cysteine (Cys)-Zn2+-indocyanine green (ICG) nanoparticles were constructed. Due to the triple-level chirality-dependent photothermal, photodynamic, and Zn2+ releasing anti-tumor effects, the d-Cys-Zn2+-ICG nanoparticles achieved 1.93 times higher anti-tumor efficiency than the l-Cys-Zn2+-ICG ones, highlighting the tremendous potential of chirality in cancer therapy. [Display omitted]