†Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
§Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States.
J Am Chem Soc. 2015 May 20;137(19):6112-5. doi: 10.1021/jacs.5b00795. Epub 2015 May 7.
The simultaneous intracellular delivery of multiple types of payloads, such as hydrophobic drugs and nucleic acids, typically requires complex carrier systems. Herein, we demonstrate a self-deliverable form of nucleic acid-drug nanostructure that is composed almost entirely of payload molecules. Upon light activation, the nanostructure sheds the nucleic acid shell, while the core, which consists of prodrug molecules, disintegrates via an irreversible self-immolative process, releasing free drug molecules and small molecule fragments. We demonstrate that the nanostructures exhibit enhanced stability against DNase I compared with free DNA, and that the model drug (camptothecin) released exhibits similar efficacy as free, unmodified drugs toward cancer cells.
同时递送达多种类型的负载物，如疏水性药物和核酸，通常需要复杂的载体系统。在此，我们展示了一种几乎完全由负载物分子组成的核酸-药物纳米结构的自递药形式。在光激活下，纳米结构会去除核酸外壳，而由前药分子组成的核心则通过不可逆的自耗蚀过程解体，释放游离药物分子和小分子碎片。我们证明，与游离 DNA 相比，纳米结构对 DNase I 具有增强的稳定性，并且释放的模型药物（喜树碱）表现出与游离、未修饰药物对癌细胞相似的疗效。
