Proton-Sponge-Coated Quantum Dots for siRNA Delivery and Intracellular Imaging

• Authors: Maksym V. Yezhelyev, Emory University; Lifeng Qi, University of Washington; Ruth O'Regan, Emory University; Shuming Nie, Emory University; Xiaohu Gao, University of Washington
• Journal Title: Journal of the American Chemical Society
• Volume: Volume 130, Number 28
• Publisher: American Chemical Society | 2008-07-16, Pages 9006-9012
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1021/ja800086u
• Subjects: Health Sciences, Oncology; Engineering, Biomedical

Abstract

We report the rational design of multifunctional nanoparticles for short-interfering RNA (siRNA) delivery and imaging based on the use of semiconductor quantum dots (QDs) and proton-absorbing polymeric coatings (proton sponges). With a balanced composition of tertiary amine and carboxylic acid groups, these nanoparticles are specifically designed to address longstanding barriers in siRNA delivery such as cellular penetration, endosomal release, carrier unpacking, and intracellular transport. The results demonstrate dramatic improvement in gene silencing efficiency by 10-20 fold and simultaneous reduction in cellular toxicity by 5-6 fold, when compared directly with existing transfection agents for MDA-MB-231 cells. The QD-siRNA nanoparticles are also dual-modality optical and electron-microscopy probes, allowing real-time tracking and ultrastructural localization of QDs during delivery and transfection. These new insights and capabilities represent a major step towards nanoparticle engineering for imaging and therapeutic applications.