Reducing the cytotoxicity while improving the anti-cancer drug loading capacity of polypropylenimine dendrimers by surface acetylation
Polypropylenimine (PPI) dendrimers have been widely used as effective deliveryvehicles for drugs and nucleic acids during the past decade. However, biomedicalapplications of PPI dendrimers were limited due to their serious cytotoxicity and lowdrug loading capacity. In the present study, acetylated PPI dendrimers with differentacetylation degrees ranged from 14.2％ to 94.3％ were synthesized and used toencapsulate drugs including methotrexate sodium, sodium deoxycholate, anddoxorubicin. Acetylated PPI dendrimers with an acetylation degree above 80％showed a significantly decreased cytotoxicity (> 90％ cell viability) on MCF-7 andA549 cells. The drug loading capacity of acetylated PPI dendrimers increasedproportionally with the acetylation degree on dendrimer surface. In addition, 94.3％acetylated PPI dendrimers exhibited a pH-responsive release profile of anticancerdrugs loaded within the nanoparticles. The cytotoxicities of methotrexate sodium anddoxorubicin on MCF-7 and A549 cells are significantly reduced when they werecomplexed with acetylated PPI dendrimers with high acetylation degrees (>80％) dueto sustained drug release from the dendrimers. The results suggest that surfaceacetylation can reduce the cytotoxicity and improve the anticancer drug loadingcapacity of cationic dendrimers, and that acetylated PPI dendrimers are promisingvehicles for anticancer drugs in clinical trials.
dendrimer, acetylation, PPI, sustained release, anticancer drug
Fei Wang Xiaopan Cai Yunzhang Su Jingjing Hu Qinglin Wu Hongfeng Zhang Jianru Xiao Yiyun Cheng
Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences,East China Normal Universi Department of Orthopedic Oncology,Changzheng Hospital,the Second Military Medical University,Shangha Department of Chemistry,University of Science and Technology of China,Hefei,Anhui,230026,P.R.China Hongkong University of Science and Technology,Hongkong,P.R.China
国内会议
2012上海市研究生学术论坛暨第三届上海交通大学医(理)工研究生学术论坛
上海
英文
1-30
2012-08-15（万方平台首次上网日期，不代表论文的发表时间）