With the advancement of RNA interference (RNAi) as a cancer therapeutic strategy, new imaging systems for effective small interfering RNA (siRNA) expression and delivery are required. Here, we describe the synthesis and characterization of multi-functional nanoparticles for simultaneous noninvasive imaging and delivery of siRNA expression constructs into tumors. These nanoparticles consisted of quantum dots (QDs) and covalently linked siRNA expression constructs targeting a gene of interest. Short hairpin RNA (shRNA) expression constructs assembled by PCR express functional siRNAs, after direct transfection into mammalian cells, bypassing the need to clone into a plasmid backbone. In addition, these nanoparticles were modified with a human amino-terminal fragment (hATF) peptide of urokinase plasminogen activator (uPA) for tumor targeting. We demonstrate the possibility for in vivo monitoring of tumor uptake of these nanoparticles by fluorescent imaging and gene silencing using bioluminescence imaging. These studies represent an important step for the advancement of new siRNA expression methods and imaging for delivery, which are essential for the development of potential cancer therapeutic agents.
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