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Article

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

Supporting Info

Maksym V. Yezhelyev^†, Lifeng Qi^‡, Ruth M. O’Regan^†, Shuming Nie ^†^§ and Xiaohu Gao ^‡

Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, Department of Bioengineering, University of Washington, William H. Foege Building N530M, Seattle, Washington 98195, and Department of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology, 101 Woodruff Circle, Suite 2001, Atlanta, Georgia 30322

J. Am. Chem. Soc., 2008, 130 (28), pp 9006–9012

DOI: 10.1021/ja800086u

Publication Date (Web): June 21, 2008

†

Winship Cancer Institute, Emory University.

‡

University of Washington.

Department of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology.

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 toward nanoparticle engineering for imaging and therapeutic applications.

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