Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.
J Am Chem Soc. 2010 Dec 8;132(48):17227-35. doi: 10.1021/ja1069932. Epub 2010 Nov 15.
Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. By introducing variations into the precursor polymer, such as molecular weight and the relative percentages of hydrophilic OEG units and hydrophobic PDS functionalities, we have achieved significant control over nanogel size. We show that the noncovalently encapsulated guest molecules can be released in response to a redox trigger, glutathione (GSH). Stability of dye encapsulation inside the nanogels and tunability in the release of guest molecules have been demonstrated through in vitro fluorescence resonance energy transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast cancer cells (MCF-7) with nanogels of different cross-linking density to demonstrate that it plays a key role in the stable encapsulation of hydrophobic drug molecules and the cell-uptake efficiencies.
由于在治疗应用中的重要意义，特别是在癌症治疗方面，能够稳定包裹药物分子并在特定触发条件下释放的纳米级载体引起了人们的极大兴趣。为此，我们合成了高度稳定的聚合物纳米凝胶，通过控制交联密度可以精细调节客体分子的释放动力学。聚合物纳米凝胶前体基于包含聚乙二醇（OEG）和吡啶二硫（PDS）单元的无规共聚物，作为侧基官能团。通过在前驱体聚合物中引入变化，如分子量和亲水性 OEG 单元与疏水性 PDS 官能团的相对百分比，我们实现了对纳米凝胶尺寸的显著控制。我们表明，非共价包裹的客体分子可以响应氧化还原触发剂谷胱甘肽（GSH）进行释放。通过体外荧光共振能量转移（FRET）实验证明了染料在纳米凝胶中的封装稳定性和客体分子释放的可调性。我们展示了不同交联密度的纳米凝胶在体外向乳腺癌细胞（MCF-7）中递送阿霉素，表明交联密度在稳定包裹疏水性药物分子和细胞摄取效率方面起着关键作用。
