State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, China.
Chem Soc Rev. 2018 Sep 17;47(18):6930-6946. doi: 10.1039/c8cs00081f.
Tumor therapeutic efficacy is determined, to a great extent, by the delivery efficiency of therapeutic drugs to their final targets. The cell nucleus has been proven to be the main interaction site for most therapeutic agents such as anticancer drugs, genes, free radicals, and heat. Therefore, it is highly expected that cell nucleus-targeting or nuclear membrane-penetrating nanotherapeutics would provide a more effective strategy than ordinary cell membrane-targeting ones for benefiting precise nanomedicine in humans' battles against cancer. This tutorial review presents a summary of the most recent progress achieved in the design, synthesis, and application of cell nucleus-targeting nanotherapeutics. We first discuss a number of design principles involved in cell nucleus-targeting nanotherapeutics, including size control, shape regulation, and surface modification. Next, we demonstrate the diverse applications of cell nucleus-targeting nanotherapeutics ranging from chemotherapy, gene therapy, photodynamic therapy, photothermal therapy to synergistic therapy. Moreover, a number of typical nanotherapeutics designed for enhanced therapeutic efficacy by targeting other subcellular organelles (such as mitochondria, lysosomes, and endoplasmic reticulum) are also briefly discussed. Finally, perspectives and challenges in this research field are proposed, in the hope of accelerating their translation into the clinic.
肿瘤的治疗效果在很大程度上取决于治疗药物到达其最终靶点的输送效率。细胞核已被证明是大多数治疗剂（如抗癌药物、基因、自由基和热）的主要相互作用部位。因此，人们高度期望细胞核靶向或核膜穿透纳米药物比普通的细胞膜靶向药物更能为人类对抗癌症的精准纳米医学提供更有效的策略。本综述介绍了细胞核靶向纳米药物的设计、合成和应用方面的最新进展。我们首先讨论了细胞核靶向纳米药物设计中涉及的一些设计原则，包括尺寸控制、形状调节和表面修饰。接下来，我们展示了细胞核靶向纳米药物的多种应用，包括化疗、基因治疗、光动力治疗、光热治疗和协同治疗。此外，还简要讨论了一些为了提高治疗效果而设计的靶向其他亚细胞细胞器（如线粒体、溶酶体和内质网）的纳米药物。最后，提出了该研究领域的观点和挑战，希望能加速其向临床转化。
