School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
J Control Release. 2017 Nov 28;266:36-46. doi: 10.1016/j.jconrel.2017.09.007. Epub 2017 Sep 8.
Cisplatin is a widely used anticancer drug in clinic. However, it may induce drug resistance after a course of treatment and it is difficult to accumulate at tumor site selectively, which result in clinic failure and side effects. We successfully bound cisplatin with vorinostat (a FDA-approved histone deacetylase inhibitor) to form a supramolecular conjugate, which can further self-assemble into nanoparticles. The nanodrug can retain in blood stream for a long time, accumulate in tumor site and hydrolyze to release the two drugs for synergistic therapy. In vivo experiments highlighted the great advantage of the supramolecular nanodrug, because it ensured the two drugs reaching cancer tissue simutaneously. Free cisplatin or cisplatin/vorinostat mixture had negligible or limited effects on A549/DR tumor growth. On the contrary, the tumor inhibitory rate approached 99% with little systemic toxicity if the dose of cisplatin-vorinostat nanodrug reached 10mg/kg body weight, thus suggesting this supramolecular nanodrug as a promising treatment of drug resistance cancer.
顺铂是一种广泛应用于临床的抗癌药物。然而，它在一个疗程后可能会产生耐药性，并且难以在肿瘤部位选择性地积累，导致临床治疗失败和副作用。我们成功地将顺铂与伏立诺他（一种 FDA 批准的组蛋白去乙酰化酶抑制剂）结合形成超分子缀合物，进一步自组装成纳米颗粒。该纳米药物可以在血液中长时间保留，在肿瘤部位积累并水解释放两种药物以协同治疗。体内实验突出了这种超分子纳米药物的巨大优势，因为它确保了两种药物同时到达癌症组织。游离顺铂或顺铂/伏立诺他混合物对 A549/DR 肿瘤生长几乎没有或有限的作用。相反，如果顺铂-伏立诺他纳米药物的剂量达到 10mg/kg 体重，肿瘤抑制率接近 99%，而全身毒性很小，这表明这种超分子纳米药物是一种有前途的耐药性癌症治疗方法。
