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

Abstract

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 d-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.