多功能共聚物-抗癌药偶联物介导靶向药物/基因共传输抗肿瘤新生血管生成治疗的研究
A multifunctional copolymer-anticancer conjugatechitosan-graft-polyethyleneimine-candesartan (CPC) containing low molecularweight chitosan(CS)backbone and polyethyleneimine(PEI)arms with candesartan(CD)conjugated via an amide bond was fabricated as a targeted co-deliverynanovector of drug and gene for potential cancer therapy. Here, CD was utilized tospecifically bind to overexpressed angiotensinⅡtypeⅠreceptor (AT1R) of tumorcells, strengthen endosomal buffering capacity of CPC and suppress tumorangiogenesis. The self-assembled CPC/pDNA complexes exhibited desirable andhomogenous particle size, moderate positive charges, superior stability, and efficientrelease of drug and gene in vitro. Flow cytometry and confocal laser scanningmicroscopy analyses confirmed that CD-targeted function and CD-enhanced bufferingcapacity induced high transfection, specific cellular uptake and efficient intracellulardelivery of CPC/pDNA complexes in AT1R-overexpressed PANC-1 cells. In addition,CPC/wt-p53 complexes co-delivering CD andsynergistic angiogenesis suppression, aswild type p53 (wt-p53) gene achievedcompared to mono-deliverymixed-deliverytumor-targetingsystems.These findings suggested that CPC could be anandidealnanovector for simultaneous transfer of drug and gene.
肿瘤新生血管生成 多功能共聚物抗癌药 物介导靶向药物 基因共传输 临床疗效
王伟 张芳榕 周建平
中国药科大学天然药物活性组分与药效国家重点实验室,药剂学教研室,童家巷24号,南京210009,中国
国内会议
石家庄
中文
1-20
2014-10-24（万方平台首次上网日期，不代表论文的发表时间）