Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
Biomaterials. 2011 Jul;32(21):4849-56. doi: 10.1016/j.biomaterials.2011.03.022. Epub 2011 Mar 31.
The combination of gene therapy and chemotherapy may increase the therapeutic efficacy in the treatment of patients. In this work, the cationic polymer prodrug/plasmid nanocomplexes were designed to in vivo synergistically treat drug-resistant breast tumors. Cationic β-cyclodextrin-polyethylenimine-Dox (PC-Dox) conjugates were prepared for carrying wt p53 plasmid in the form of PC-Dox/p53 nanocomplexes to achieve synergistic cancer therapeutic effects of drug and gene therapies. Such PC-Dox/p53 nanocomplexes ensure that both drug and gene can be delivered to the same cancer cells. The physicochemical properties and Dox release profiles of the PC-Dox conjugates, as well as their antitumor activities in vitro and in vivo, were determined. mRNA expression and western blot experiments also proved that co-delivery of Dox with wt p53 plasmid from PC-Dox/wt p53 complexes could promote wt p53 gene expression largely. By investigating anticancer efficacy via multi-drug resistant MCF-7/Adr breast cancer cells, it was found that PC-Dox/wt p53 complexes promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. With the efficient ability to co-deliver drug and gene, such multifunctional PC-Dox/pDNA complexes should have great potential applications in cancer therapy.
基因治疗与化疗的联合应用可能会提高患者治疗的疗效。在这项工作中，设计了阳离子聚合物前药/质粒纳米复合物，以协同体内治疗耐药性乳腺癌。阳离子β-环糊精-聚乙二醇亚胺-阿霉素（PC-Dox）缀合物被制备用于以 PC-Dox/p53 纳米复合物的形式携带 wt p53 质粒，以实现药物和基因治疗的协同癌症治疗效果。这种 PC-Dox/p53 纳米复合物确保药物和基因都可以递送到相同的癌细胞中。测定了 PC-Dox 缀合物的理化性质和阿霉素释放曲线，以及它们在体外和体内的抗肿瘤活性。mRNA 表达和 Western blot 实验也证明，从 PC-Dox/wt p53 复合物共递送阿霉素与 wt p53 质粒可以显著促进 wt p53 基因的表达。通过研究多药耐药 MCF-7/Adr 乳腺癌细胞的抗癌疗效，发现 PC-Dox/wt p53 复合物促进了体内肿瘤生长的抑制作用，并延长了荷瘤小鼠的生存时间。由于具有高效共递药和基因的能力，这种多功能 PC-Dox/pDNA 复合物在癌症治疗中应该具有很大的应用潜力。
