2007 NSTI Nanotechnology Conference and Trade Show - Nanotech 2007 - 10th Annual

Development of Boneseeking Gold Nanoparticles for Imaging

S.K. Nune, R. Kannan and K.V. Katti
University of Missouri-columbia, US

bisphosphonates, neridronate, gold nanoparticles, calcium hydroxyapatite

There is significant clinical demand for the development of new and novel methods for highly sensitive, accurate and economically viable detection and treatment protocols for cancer. Herein, we report our results on the synthesis of modified bisphosphonate (Nedridronate) and bioconjugation protocols with gold nanoparticles for potential molecular imaging applications. We also report the results on the in-vitro stability studies including uptake with bone-mimicking calcium hydroxyapatite. Incorporation of AuNPs on the bisphophonate frame work was recently achieved in our laboratories. We successfully synthesized the lipoic acid conjugated Neridronate (Lip-Bisphos) by the reaction of lipoic acid anhydride and Neridronate in the presence of 40 % NaOH in water and 1,4-dioxane (80:15) at refluxing conditions. Starch stabilized gold nanoparticles (SAuNP’s) bearing both excellent optical sensitivity and stability which were used for bioconjugation were prepared by the method developed in our laboratory.2 The SAuNP’s were purified by filtering through the Sephedex G-100 column and were conjugated with the Lip-Bisphos by stirring both the solutions in water for 72 hours at room temperature to obtain Au-Lip-Bisphos. The Au-Lip-Bisphos particles showed a narrow distribution and are characterized by TEM, UV-visible spectroscopy and SEM/EDS techniques. We further carried out the in vitro stability studies with 0.5 % cysteine, 25 % NaCl solution and buffers (pH 1,3,5,7 and 9). We further performed the bone mimicking in-vitro experiments with the calcium hydroxyapatite. Calcium hydroxyapatite is a non-toxic bone building food and is a most absorbable form of calcium and helps to reduce bone loss. Our in-vitro experiments have clearly shown that >99% of Au-Lip-Bisphos (bone seeking gold nanoparticles) bind to calcium hydroxyapatite whereas the normal SAuNP’s (starch stabilized gold nanoparticles) did not bind. These results clearly demonstrate the efficiency of the Au-Lip-Bisphos to bind to bone surface.

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