title: Reducing cytotoxicity while improving anti-cancer drug loading capacity of polypropylenimine dendrimers by surface acetylation.
abstract: Polypropylenimine (PPI) dendrimers have been widely used as effective delivery vehicles for drugs and nucleic acids during the past decade. However, biomedical applications of PPI dendrimers were limited because of their serious cytotoxicity and low drug loading capacity. In the present study, acetylated PPI dendrimers with different degrees of acetylation ranging from 14.2% to 94.3% were synthesized and used to encapsulate drugs, including methotrexate sodium, sodium deoxycholate and doxorubicin. Acetylated PPI dendrimers with a degree of acetylation >80% showed a significantly decreased cytotoxicity (>90% cell viability) on MCF-7 and A549 cells. The drug loading capacity of acetylated PPI dendrimers increased proportionally with the degree of acetylation on the dendrimer surface. In addition, 94.3% acetylated PPI dendrimers exhibited a pH-responsive release profile of anticancer drugs loaded within the nanoparticles. The cytotoxicities of methotrexate sodium and doxorubicin on MCF-7 and A549 cells were significantly reduced when they were complexed with acetylated PPI dendrimers with high degrees of acetylation (>80%), owing to sustained drug release from the dendrimers. The results suggest that surface acetylation can reduce the cytotoxicity and improve the anticancer drug loading capacity of cationic dendrimers, and that acetylated PPI dendrimers are promising vehicles for anticancer drugs in clinical trials.
authors: Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors: Fei
authors: F
authors: Wang
authors: Xiaopan
authors: X
authors: Cai
authors: Yunzhang
authors: Y
authors: Su
authors: Jingjing
authors: J
authors: Hu
authors: Q
authors: Q
authors: Wu
authors: Hongfeng
authors: H
authors: Zhang
authors: Jianru
authors: J
authors: Xiao
authors: Yiyun
authors: Y
authors: Cheng
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D011126:Polypropylenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D050091:Dendrimers; D011126:Polypropylenes; C443641:poly(propyleneimine)