Dual Signals of Chiral and Fluorescent Copper Sulphide Nanoparticles Boost Tumor Cell Autophagy

Abstract Autophagy is a key regulator in a diverse range of human diseases. Here, chiral copper sulfide (CuS) nanoparticles (NPs) modified with penicillamine are fabricated, which exhibited a circular dichroism (CD) spectrum between 300 and 1000 nm and a fluorescence peak at 680 nm. The experimental data showed that D ‐CuS NPs exhibited chirality‐dependent autophagy induction, outperforming L ‐CuS NPs, and targeted breast cancer cells with 228.4 times higher affinity for CD81 receptor. The mechanism is revealed that chiral NPs specifically bound to CD81 receptor to open mechanosensitive calcium channels and motivated the calmodulin‐dependent protein kinase kinase β (CaMKKβ)/AMPK pathway, which enhanced Atg1/Unc‐51‐like autophagy activating kinase 1 (ULK1) activity to promote autophagy. In vivo experiments confirmed the selective accumulation of D ‐CuS NPs in tumors, induction of autophagy, and successful treatment of the tumor. Therefore, chiral CuS NPs show great potential for modulating biological processes and improving tumor treatment.