Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 130, Issue 28, Pages 9006-9012Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja800086u
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Funding
- NCI NIH HHS [U54 CA119338, R01 CA108468, U54 CA119338-03, U54CA119338, R01 CA131797, R01 CA131797-02] Funding Source: Medline
- NHLBI NIH HHS [U01HL080711, U01 HL080711] Funding Source: Medline
- NIGMS NIH HHS [P20 GM072069] Funding Source: Medline
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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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