Porphyrin-based supramolecular chiral assembly for enantioselective interaction and augmented photodynamic therapy

Supramolecular chiral assemblies are mostly studied as drug carriers because of their enantioselective interaction with biological systems. However, this approach may compromise chirality-dependent therapeutic efficacy and potentially underestimate the significance of chirality in nanomedicine. Herein, supramolecular chiral nanoparticles, D/L-arginine (Arg)-meso-tetra(4-carboxyphenyl) porphine (TCPP), were constructed through the self-assembly of D/L-Arg and TCPP. Owing to the interaction between D/L-Arg and TCPP, chirality transfer from D/L-Arg to TCPP was observed, which resulted in the direct chiral induction of TCPP within supramolecular assemblies. Furthermore, driven by enantioselective interaction with proteins, D-Arg-TCPP demonstrated 1.5-fold greater cellular uptake efficiency than L-Arg-TCPP via caveolin-dependent endocytosis. Thus, the enantiomer-dependent reactive oxygen species (ROS) generating capacity-induced photodynamic anti-tumor performance, with D-Arg-TCPP exhibiting 1.9 times higher efficacy than L-Arg-TCPP, was verified. Our findings not only elucidate the mechanisms underlying chirality-dependent behavior of porphyrin-based supramolecular assemblies, but also pave a new avenue for optimizing chirality-mediated cancer therapy.