Endosomolytic reducible polymeric electrolytes for cytosolic protein delivery.
Endosomolytic reducible polymeric electrolytes for cytosolic protein delivery.
复制标题
DOI：
10.1021/bm400337f
复制
发表时间：
2013-08-12
影响因子：
6.2
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Tian, Li;Kang, Han Chang;Bae, You Han
尽管蛋白质在胞质中具有许多重要的功能，但与质膜相比，蛋白质药物向胞质的递送受到的关注较少。为了解决这个问题，并有效地将带电蛋白质递送到细胞质中，我们使用内体溶解的硫醇触发的可降解聚电解质作为载体。通过硫醇化支化聚乙烯亚胺（bPEI）的氧化聚合反应，合成了阳离子型可还原的聚乙烯基吡咯烷酮（RPC-bPEI）0. 8 kDa 2。通过引入羧酸将聚合物转化为阴离子的、可还原的PANRPA-bPEI 0. 8 kDa 2。两种可还原的聚电解质（RPC-bPEI 0. 8 kDa 2和RPA-bPEI 0. 8 kDa 2）与带相反电荷的模型蛋白（牛血清白蛋白（BSA）和溶菌酶（LYZ））复合，以重量比（WR）≥ 1形成尺寸小于200 nm的BSA/蛋白复合物。所得到的复合物保持质子缓冲能力几乎相当于在蛋白质络合的情况下的聚电解质，并与MCF 7人乳腺癌细胞的细胞相容性。在模拟胞质溶胶的富巯基条件下，RPC-bPEI 0. 8 kDa 2/BSA和RPA-bPEI 0. 8 kDa 2/LYZ复合物的大小显著增加，并释放负载的蛋白质，而不像蛋白质复合物与不可还原的聚电解质（bPEI 25 kDa和bPEI 25 kDaCOOH）。的ESTA/蛋白质复合物表现出类似的细胞摄取相应的蛋白质单独，但前者允许更多的蛋白质逃逸到胞质溶胶从内溶酶体比后者作为一个结果的内体溶解功能的聚电解质。此外，蛋白质/蛋白质复合物中的蛋白质保持其固有的二级结构。总之，结果显示了所设计的内体溶解性、可还原的聚电解质用于将蛋白质递送至胞质溶胶的潜力。
Despite the numerous vital functions of proteins in the cytosolic compartment, less attention has been paid to the delivery of protein drugs to the cytosol than to the plasma membrane. To address this issue and effectively deliver charged proteins into the cytoplasm, we used endosomolytic, thiol-triggered degradable polyelectrolytes as carriers. The cationic, reducible polyelectrolyte RPC-bPEI0.8kDa2 was synthesized by the oxidative polymerization of thiolated branched polyethyleneimine (bPEI). The polymer was converted to the anionic, reducible polyelectrolyte RPA-bPEI0.8kDa2 by introducing carboxylic acids. The two reducible polyelectrolytes (RPC-bPEI0.8kDa2 and RPA-bPEI0.8kDa2) were complexed with counter-charged model proteins (bovine serum albumin (BSA) and lysozyme (LYZ)), forming polyelectrolyte/protein complexes of less than 200 nm in size at weight ratios (WR) of ≥ 1. The resultant complexes maintained a proton buffering capacity nearly equivalent to that of the polyelectrolytes in the absence of protein complexation and were cytocompatible with MCF7 human breast carcinoma cells. Under cytosol-mimicking thiol-rich conditions, RPC-bPEI0.8kDa2/BSA and RPA-bPEI0.8kDa2/LYZ complexes increased significantly in size and released the loaded protein, unlike the protein complexes with non-reducible polyelectrolytes (bPEI25kDa and bPEI25kDaCOOH). The polyelectrolyte/protein complexes showed similar cellular uptake to the corresponding proteins alone, but the former allowed more protein to escape into the cytosol from endolysosomes than the latter as a result of the endosomolytic function of the polyelectrolytes. In addition, the proteins in the polyelectrolyte/protein complexes kept their intrinsic secondary structures. In conclusion, the results show the potential of the designed endosomolytic, reducible polyelectrolytes for the delivery of proteins to the cytosol.
登录
查看更多内容
影响因子：
14
作者：
Kang, Han Chang;Kang, Ho-Jung;Bae, You Han
通讯作者：
Bae, You Han
影响因子：
10.8
作者：
Gary, Dana J.;Puri, Nitin;Won, You-Yeon
通讯作者：
Won, You-Yeon
影响因子：
64.8
作者：
CRICK, F
通讯作者：
CRICK, F
影响因子：
6.2
作者：
Hwang HS;Kang HC;Bae YH
通讯作者：
Bae YH
影响因子：
2.9
作者：
GREENFIE.N;FASMAN, GD
通讯作者：
FASMAN, GD