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

en This link goes to a English section zh This link goes to a Chinese section 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. 摘要 en This link goes to a English section zh This link goes to a Chinese section 手性CdSe/CdS量子点 ( QDs ) 因具有光致发光及光催化活性 , 在肿瘤荧光成像 ( FLI ) 与光动力治疗 ( PDT ) 中具有广阔应用前景。然而 , QDs几何参数 , 特别是长径比 ( AR ) 与其诊疗性能的构效关系尚未得到系统研究。本研究通过手性半胱氨酸 ( D-/L-Cys ) 修饰 , 制备了多种具有超薄壳层手性CdSe/CdS核壳点-棒纳米结构 ( DRs ) , 系统探讨了调控AR对其在乳腺癌细胞中FLI及PDT性能的影响。本研究构建并表征了四组核心尺寸与壳层厚度相近、但AR各异的 ( AR: 3.2, 4.6, 6.7, 14.3 ) D-/L-构型CdSe/CdS DRs ( D/L-DRs ) , 并在乳腺癌细胞系及荷瘤小鼠模型中系统评估其成像与治疗效果。研究结果证明 , D-/L-Cys修饰显著提升了CdSe/CdS DRs的生物相容性 , 并增强了PDT效果。AR的变化可调控D/L-DRs的FLI性能 ( Ex : 561 nm ; Em : 570–620 nm ) 和圆偏振光 ( CPL ) 激发的活性氧 ( ROS ) 产率 : 具有较小AR的D/L-DRs 在肿瘤细胞内表现出更强的荧光信号和更高的单位AR下的ROS 产率 , 显示出更优的诊疗性能。此外 , D-Cys修饰的CdSe/CdS-DRs在体内外的成像亮度显著高于L-构型 , 提示手性特性影响纳米材料更易于被肿瘤细胞摄入。473 nm CPL激发下 , 由D/L-DRs介导的PDT可通过ROS激活肿瘤细胞自噬 , 导致自噬依赖性的细胞死亡实现肿瘤治疗。综上 , 本研究阐明了QDs的AR与其诊疗性能间的构效关系 , 证实了物理几何结构与手性修饰在实现肿瘤诊疗中的协同作用 , 为设计开发下一代兼具优异光学、生物学及治疗功能的手性纳米材料提供了新的依据。