Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea.
Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
Biomaterials. 2016 Jan;75:102-111. doi: 10.1016/j.biomaterials.2015.10.022. Epub 2015 Oct 14.
We present a cationic polymer architecture composed of phenylboronic acid (PBA), sugar-installed polyethylenimine (PEI), and polyethylene glycol (PEG). The chemical bonding of PBA with the diol in the sugar enabled the crosslinking of low-molecular-weight (MW) PEI to form high-MW PEI, resulting in strong interaction with anionic DNA for gene delivery. Inside the cell, the binding of PBA and sugar was disrupted by either acidic endosomal pH or intracellular ATP, so gene payloads were released effectively. This dual stimuli-responsive gene release drove the polymer to deliver DNA for high transfection efficiency with low cytotoxicity. In addition, PBA moiety with PEGylation facilitated the binding of polymer/DNA polyplexes to sialylated glycoprotein which is overexpressed on the tumor cell membrane, and thus provided high tumor targeting ability. Therapeutic application of our polymer was demonstrated as an anti-angiogenic gene delivery agent for tumor growth inhibition. Our judicious designed polymer structure based on PBA provides enormous potential as a gene delivery agent for effective gene therapy by stimuli-responsiveness and tumor targeting.
我们提出了一种由苯硼酸（PBA）、糖基化聚亚乙基亚胺（PEI）和聚乙二醇（PEG）组成的阳离子聚合物结构。PBA 与糖中的二醇的化学键合使得低分子量（MW）PEI 交联形成高分子量（MW）PEI，从而与阴离子 DNA 形成强烈的相互作用以进行基因传递。在细胞内，PBA 和糖的结合被酸性内涵体 pH 或细胞内 ATP 破坏，因此有效释放了基因负载物。这种双重刺激响应性基因释放促使聚合物为高转染效率和低细胞毒性传递 DNA。此外，PEG 化的 PBA 部分有助于聚合物/DNA 复合物与肿瘤细胞膜上过表达的唾液酸化糖蛋白结合，从而提供了高肿瘤靶向能力。我们的聚合物的治疗应用被证明是一种抗血管生成基因递送剂，可抑制肿瘤生长。我们基于 PBA 的明智设计的聚合物结构为通过刺激响应性和肿瘤靶向进行有效的基因治疗提供了作为基因递送剂的巨大潜力。
