Aspect Ratio‐Controlled Chiral Nanostructures for Dual‐Mode Breast Cancer Theranostics

ABSTRACT Chiral CdSe/CdS quantum dots (QDs) have emerged as promising platforms for precise cancer diagnosis and therapy due to their unique optical properties and biological interactions. In this study, we systematically investigated the role of aspect ratio (AR) modulation in ultrathin‐shelled chiral CdSe/CdS dot‐in‐rods (DRs) on their performance in fluorescence imaging (FLI) and photodynamic therapy (PDT) against breast cancer. Four groups of chiral CdSe/CdS DRs (D/L‐DRs) with comparable core sizes and shell thicknesses but distinct ARs were synthesized and characterized. Surface modification with chiral cysteine not only ensured the biocompatibility of D/L‐DRs but also conferred enhanced chiroptical activity. Notably, D/L‐DR‐1, featuring the smallest AR, not only exhibited excellent reactive oxygen species (ROS) production efficiency upon circularly polarized light (CPL) irradiation but also achieved the most efficient FLI performance. Among them, D‐enantiomer modified CdSe/CdS DRs showed higher imaging brightness both in vitro and in vivo. Mechanistically, CPL‐triggered ROS production by D/L‐DRs could activate autophagy, leading to autophagy‐dependent tumor cell death. In vivo experiments also confirmed that D‐DR‐1 mediated PDT achieved complete tumor ablation in 80% of treated mice. This study establishes a clear structure‐activity relationship between AR of QDs and functional performance, further highlighting the dual contribution of physical geometry and chirality in enabling selective and effective tumor theranostics. These insights offer new design principles for next‐generation chiral nanomaterials with optimized optical, biological, and therapeutic functionalities.