Nuclear delivery of dual anticancer drug-based nanomedicine constructed by cisplatinum-induced peptide self-assembly
Tengyan Xu, Chunhui Liang, Debin Zheng, Xiaorong Yan, Yaoxia Chen, Yumiao Chen, Xinxin Li, Yang Shi, Ling Wang, Zhimou Yang
Abstract
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.