当前位置:> 首页 > 论文著作 > 正文
The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes
作者:Liu, G. J.; Ma, S. B.; Li, S. K.; Cheng, R.; Meng, F. H.; Liu, H. Y.; Zhong, Z. Y.
关键字:polymersomes, protein delivery, cancer therapy
论文来源:期刊
具体来源:Biomaterials 2010, 31, 7575-7585.
发表时间:2010年

Biodegradable chimaeric polymersomes based on asymmetric PEG-PCL-PDEA triblock copolymers were prepared and investigated for delivery of exogenous proteins into cells. PEG-PCL-PDEA copolymers with Mn PEG = 5 kg/mol, Mn PCL = 18.2 kg/mol, and short PDEA blocks ranging from 1.1, 2.7 to 4.1 kg/mol (denoted as copolymer 1, 2 and 3, respectively) were obtained by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. The direct hydration of copolymer thin films in MES buffer (pH 5.3) yielded uniform polymersomes with sizes of 130–175 nm. These polymersomes had close to neutral zeta potentials (−2 not, vert, similar +2.7 mV) at pH 7.4. The polymersomal structures were confirmed by confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and catalytic activity experiment on 3,3′,3″-phosphinidyne(trisbenzenesulfonic acid)-loaded polymersomes. MTT assays showed that these polymersomes were non-toxic up to a concentration of 0.5 mg/mL. These chimaeric polymersomes, in particular polymersome 2, showed remarkably high protein loading efficiencies and loading contents for bovine serum albumin (BSA), cytochrome C (CC), lysozyme (Lys), ovalbumin (OVA) and immunoglobulin G (IgG). The encapsulation of proteins did not significantly alter the polymersome size distributions and zeta potentials. The protein release studies showed that both BSA and CC were released in a controlled manner. Importantly, the released CC fully maintained its activity. Notably, CLSM studies showed that FITC-CC loaded polymersomes efficiently delivered and released proteins into the cytoplasm of RAW 264.7 cells. Moreover, these chimaeric polymersomes were able to simultaneously load and transport proteins and doxorubicin into the cytoplasm as well as the cell nucleus. We are convinced that these biodegradable chimaeric polymersomes have great potentials in protein therapy.