Silver Nanoscale Antisense Drug Delivery System for Photoactivated Gene Silencing
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- 作者：Paige K. Brown ; Ammar T. Qureshi ; Alyson N. Moll ; Daniel J. Hayes ; W. Todd Monroe
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：April 23, 2013
- 年：2013
- 卷：7
- 期：4
- 页码：2948-2959
- 全文大小：628K
- 年卷期：v.7,no.4(April 23, 2013)
- ISSN：1936-086X
文摘
The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60鈥?0 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies.