Asadi Hamed, Khoee Sepideh
Polymer Laboratory, Chemistry Department, School of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran.
Polymer Laboratory, Chemistry Department, School of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran.
Int J Pharm. 2016 Sep 10;511(1):424-435. doi: 10.1016/j.ijpharm.2016.07.037. Epub 2016 Jul 18.
Nanosized polymeric delivery systems that encapsulate drug molecules and release them in response to a specific intracellular stimulus are of promising interest for cancer therapy. Here, we demonstrated a simple and fast synthetic protocol of redox-responsive nanogels with high drug encapsulation efficiency and stability. The prepared nanogels displayed narrow size distributions and versatility of surface modification. The polymer precursor of these nanogels is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. The nanogels were prepared through a lock-in strategy in aqueous media via self cross-linking of PDS groups. By changing polymer concentration, we could control the size of nanogels in range of 80-115nm. The formed nanogels presented high doxorubicin (DOX) encapsulation efficiency (70% (w/w)) and displayed pH and redox-controlled drug release triggered by conditions mimicking the reducible intracellular environment. The nanogels displayed an excellent cytocompatibility and were effectively endocytosed by A2780CP ovarian cancer cells, which make them promising nanomaterials for the efficient intracellular delivery of anticancer drugs.
能够包裹药物分子并根据特定细胞内刺激释放药物的纳米级聚合物递送系统在癌症治疗方面具有广阔的应用前景。在此，我们展示了一种简单快速的合成氧化还原响应性纳米凝胶的方法，该纳米凝胶具有高药物包封效率和稳定性。制备的纳米凝胶呈现出窄的尺寸分布和表面修饰的多功能性。这些纳米凝胶的聚合物前体基于一种无规共聚物，其含有作为侧链官能团的低聚乙二醇（OEG）和吡啶二硫醚（PDS）单元。纳米凝胶通过在水性介质中通过PDS基团的自交联采用锁定策略制备。通过改变聚合物浓度，我们可以将纳米凝胶的尺寸控制在80 - 115nm范围内。形成的纳米凝胶呈现出高的阿霉素（DOX）包封效率（70%（w/w）），并在模拟可还原细胞内环境的条件下表现出pH和氧化还原控制的药物释放。这些纳米凝胶表现出优异的细胞相容性，并被A2780CP卵巢癌细胞有效内吞，这使其成为用于高效细胞内递送抗癌药物的有前景的纳米材料。
