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Light-Triggered, Self-Immolative Nucleic Acid-Drug Nanostructures

2015; American Chemical Society; Volume: 137; Issue: 19 Linguagem: Inglês

10.1021/jacs.5b00795

1943-2984

Xuyu Tan, Ben B. Li, Xueguang Lu, Fei Jia, Clarissa Santori, Priyanka Menon, Hui Li, Bohan Zhang, Jean J. Zhao, Ke Zhang,

DNA and Nucleic Acid Chemistry

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.