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Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells
Authors:Amanda L. Martin   Jennifer L. Hickey   Amber L. Ablack   John D. Lewis   Leonard G. Luyt  Elizabeth R. Gillies
Affiliation:(1) Department of Chemistry, The University of Western Ontario, 1151 Richmond St., London, ON, N6A 5B7, Canada;(2) Department of Chemical and Biochemical Engineering, The University of Western Ontario, 1151 Richmond St., London, ON, N6A 5B7, Canada;(3) Department of Oncology, The University of Western Ontario, 1151 Richmond St., London, ON, N6A 5B7, Canada;(4) Department of Medical Imaging, The University of Western Ontario, 1151 Richmond St., London, ON, N6A 5B7, Canada;(5) Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond St., London, ON, N6A 5B7, Canada;
Abstract:
The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [β-Ala11, Phe13, Nle14]bombesin-(7–14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.
Keywords:
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