一种活性氧（ROS）响应性聚合物，用于在癌细胞中进行安全、高效和靶向的基因递送。
A reactive oxygen species (ROS)-responsive polymer for safe, efficient, and targeted gene delivery in cancer cells.
机构信息
The Wallace H. Coulter Department of Biomedical Engineering, School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.
出版信息
Angew Chem Int Ed Engl. 2013 Jul 1;52(27):6926-9. doi: 10.1002/anie.201209633. Epub 2013 May 28.
Abstract
The high intracellular oxidative stress in a cancer cell is a biologically relevant stimulus for efficient intracellular delivery of therapeutic genes. In this study, reactive oxygen species (ROS)-responsive poly(amino thioketal) (PATK) was synthesized to achieve efficient and safe intracellular gene delivery in prostate cancer cells. The DNA/PATK polyplexes were efficiently disassembled upon exposure to high levels of ROS in prostate cancer cells, leading to enhanced intracellular release of DNA in the cells. As a result, DNA/PATK polyplexes showed significantly higher gene transfection efficiency than their non-degradable counterparts did. In addition, conjugation of GRP78 protein-targeting peptide to the PATK not only increased its cellular uptake in prostate cancer cells but also enhanced gene transfection efficiency. This study demonstrates that ROS-responsive PATK functionalized with a cancer-targeting peptide is a promising gene carrier for safe, efficient, and cancer-targeted gene delivery.
摘要
在癌细胞中，高水平的细胞内氧化应激是实现治疗基因有效胞内递送的生物学相关刺激因素。在这项研究中，合成了活性氧（ROS）响应性聚（氨基硫代缩醛）（PATK），以实现前列腺癌细胞中高效和安全的细胞内基因递送。DNA/PATK 超分子复合物在暴露于高水平 ROS 的前列腺癌细胞中可有效解组装，导致 DNA 在细胞内的释放增强。结果，DNA/PATK 超分子复合物的基因转染效率明显高于不可降解的对照物。此外，将 GRP78 蛋白靶向肽连接到 PATK 上，不仅增加了其在前列腺癌细胞中的细胞摄取，还增强了基因转染效率。本研究表明，用癌症靶向肽功能化的 ROS 响应性 PATK 是一种有前途的基因载体，可用于安全、高效和癌症靶向的基因递送。
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