Xu Tengyan, Liang Chunhui, Zheng Debin, Yan Xiaorong, Chen Yaoxia, Chen Yumiao, Li Xinxin, Shi Yang, Wang Ling, Yang Zhimou
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, P. R. China.
Nanoscale. 2020 Jul 28;12(28):15275-15282. doi: 10.1039/d0nr00143k. Epub 2020 Jul 9.
Nuclear delivery of anticancer drugs, particularly dual complementary anticancer drugs, can significantly improve chemotherapy efficacy. However, successful examples are rare. We reported a novel dual anticancer drug-based nanomedicine with nuclear accumulation properties. The nanomedicine was formed by chelation between a drug peptide amphiphile Rh-GFFYERGD (Rh represents Rhein, 1,8-dihydroxy-3-carboxy anthraquinonea) and cisplatinum (Pt). A single molecule of the drug peptide amphiphile could chelate up to 8 equiv. of cisplatinum in the resulting nanofibers. The nanofibers with a 1 : 4 ratio of Rh-GFFYERGD to cisplatinum demonstrated remarkable cellular uptake, and more significantly, superior nuclear accumulation properties. Additionally, the nanofibers could also bind to the DNA molecule more efficiently than those formed by the drug peptide amphiphile. Thus the nanofibers exhibited excellent anticancer properties both in vitro and in vivo. We envision a significant therapeutic potential of the dual anticancer drug-based nanomedicine with cisplatinum in cancer.
抗癌药物的细胞核递送，尤其是双重互补抗癌药物的细胞核递送，可显著提高化疗疗效。然而，成功的例子很少。我们报道了一种具有核积累特性的新型基于双重抗癌药物的纳米药物。该纳米药物是由药物肽两亲物Rh-GFFYERGD（Rh代表大黄酸，1,8-二羟基-3-羧基蒽醌）和顺铂（Pt）之间的螯合作用形成的。在所得纳米纤维中，单个药物肽两亲物分子最多可螯合8当量的顺铂。Rh-GFFYERGD与顺铂比例为1∶4的纳米纤维表现出显著的细胞摄取，更重要的是，具有优异的核积累特性。此外，与由药物肽两亲物形成的纳米纤维相比，这些纳米纤维还能更有效地与DNA分子结合。因此，这些纳米纤维在体外和体内均表现出优异的抗癌特性。我们设想基于双重抗癌药物和顺铂的纳米药物在癌症治疗中具有巨大的治疗潜力。
