Nuclear Mapping of Nanodrug Delivery Systems in Dynamic Cellular Environments

Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemodrugs is important to predict the success of the nanoformulation. In this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemodrug across the cell membrane. The algorithm helped map free drug and drug-loaded nanoparticles, revealing a varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and -resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region, while the drug accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin.纳米制剂（nanoformulations）在化疗药物递送领域已展现出显著应用潜力，且具备极高的临床研究价值。然而，精准定位化疗药物的细胞核分布，是预测纳米制剂治疗效果的核心前提。本研究借助荧光显微镜技术与亚细胞追踪算法，对化疗药物在癌细胞内的扩散行为进行了可视化定位分析。实验结果显示，带正电纳米颗粒可高效介导化疗药物穿透细胞膜；该算法可同时追踪游离药物与载药纳米颗粒，进而在活细胞的动态环境中，揭示化疗药物在药物敏感型与耐药型癌细胞内存在迥异的细胞核扩散模式：药物敏感型癌细胞内的药物摄取量随时间呈指数级增长，而耐药型癌细胞内的药物分布则呈现随机且不对称的特征。此外，载药纳米颗粒主要滞留于核周区域，而游离药物则会在细胞核内大量蓄积。本研究采用的追踪方法，可有效预测不同剂型多柔比星（doxorubicin）纳米制剂的临床治疗效果。