Different internalization pathways of polymeric micelles and unimers and their effects on vesicular transport.
Different internalization pathways of polymeric micelles and unimers and their effects on vesicular transport.
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DOI：
10.1021/bc8002315
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发表时间：
2008-10
影响因子：
4.7
通讯作者：
Kabanov, Alexander V.
中科院分区：
文献类型：
--
作者：
Sahay, Gaurav;Batrakova, Elena V.;Kabanov, Alexander V.
合成聚合物在细胞内的有效进入是聚合物药物递送中的中心问题。虽然聚合物被广泛认为与质膜非特异性相互作用，我们提出了意想不到的证据表明，两亲性嵌段共聚物取决于它们的聚集状态可以区分小窝或网格蛋白介导的内吞作用。聚（环氧乙烷）（PEO）和聚（环氧丙烷）（PPO）的嵌段共聚物Pluronic® P85（P85），在低于临界胶束浓度（CMC）时作为单分子线团（单聚体）存在，而在高于CMC时形成具有疏水性PPO核和亲水性PEO壳的14.6 nm聚集胶束。使用内吞作用抑制剂和与内吞作用标记物（网格蛋白特异性抗体和转铁蛋白用于网格蛋白和小窝蛋白-1特异性抗体和霍乱毒素B用于小窝）共定位来阐明哺乳动物细胞中P85的内化途径。总之，我们的研究结果表明，P85单聚体通过小窝介导的内吞内化，而P85胶束通过网格蛋白介导的内吞内化。此外，在高于0.01%的浓度下，P85抑制小窝介导的内吞作用（霍乱毒素B），而对网格蛋白介导的内吞作用（转铁蛋白）几乎没有影响或没有影响。Pluronic®与小窝的选择性相互作用可以解释其显著的药理活性，包括抑制药物外排转运、激活基因表达和剂量依赖性高脂血症。
Efficient entry of synthetic polymers inside cells is a central issue in polymeric drug delivery. Though polymers are widely believed to interact non-specifically with plasma membrane we present unexpected evidence that amphiphilic block copolymers depending on their aggregation state can distinguish between caveolae- or clathrin-mediated endocytosis. A block copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronic® P85 (P85), below critical micelle concentration (CMC) exists as single molecule coils (unimers) and above CMC forms 14.6 nm aggregated micelles with hydrophobic PPO core and hydrophilic PEO shell. The internalization pathways of P85 in mammalian cells were elucidated using endocytosis inhibitors and co-localization with endocytosis markers (clathrin-specific antibodies and transferrin for clathrin and caveolin-1-specific antibodies and cholera toxin B for caveolae). All together, our results indicate that P85 unimers internalize through caveolae-mediated endocytosis, while P85 micelles internalize through clathrin-mediated endocytosis. Furthermore, at concentrations above 0.01% P85 inhibits caveolae-mediated endocytosis (cholera toxin B), while having little or no effect on the clathrin-mediated endocytosis (transferrin). Selective interaction of Pluronic® with caveolae may explain its striking pharmacological activities including inhibition of drug efflux transport, activation of gene expression and dose-dependent hyperlipidemia.
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突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
7.8
作者：
Damke, H;Baba, T;Warnock, D E;Schmid, S L
通讯作者：
Schmid, S L
影响因子：
3.7
作者：
Batrakova, EV;Han, HY;Kabanov, AV
通讯作者：
Kabanov, AV
影响因子：
5.3
作者：
Jones AT
通讯作者：
Jones AT
影响因子：
3.7
作者：
Batrakova, EV;Han, HY;Kabanov, AV
通讯作者：
Kabanov, AV
影响因子：
8.8
作者：
Batrakova EV;Li S;Elmquist WF;Miller DW;Alakhov VY;Kabanov AV
通讯作者：
Kabanov AV