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Multi-Functional Superparamagnetic Iron Oxide Particles as Cancer Therapeutic Agents

By P.M. Gannett, J.A. Barr, R.L. Carroll, S.L. Yedlapalli and A. Narayanan

Abstract

Superparamagnetic iron-oxide nanoparticles (SPIONs) are magnetic nanoparticles may be useful for early detection and treatment of cancers. SPIONs provide therapeutic drug-loading capabilities and targeting specificity through the use of antibodies or receptor specific tags. These versatile particles are prime candidates for improving current means to the treatment of cancer and potentially other diseases. This multi-disciplinary project includes various milestones and multiple aims: i) identify and optimize SPION design parameters that optimize aqueous stability and maximize amphiphilic character, ii) evaluate SPION drug storage and release characteristics, and iii) demonstrate binding and entry into targeted cells. The specific aim of this project is the coupling of cell-specific targeting agents to SPIONs. An antisense oligonucleotide against Survivin mRNA was synthesized by solid-phase DNA synthesis with an amino-terminated linker on the 3' end (5'CCCAGCCTTCCAGCTCCTTG-(CH2)6-3'NH2). SPIONs were prepared and then coated with a copolymer containing surface carboxylic acid groups (-COOH). The carboxylic acid groups were activated by treatment with N-((3-dimethylamino)-propyl)-Nethyl carbodiimide and coupled to oligonucleotides via the –NH2 terminus to the –COOH groups resulting in the formation of an amide linkage between the –COOH groups of the SPION and the –NH2 of the antisense oligonucleotide. Circular dichroism (CD) studies were performed to quantify/optimize coupling and to demonstrate antisense Survivin duplex formation was not inhibited by the presence of the SPION. CD results were correlated with agarose gel electrophoresis data and demonstrated oligonucleotides coupling to the SPION and that the SPION did not significantly alter duplex formation. Future studies will target cellular absorption and antisense binding to Survivin mRNA using confocal microscopy (Supported, in part, from NIH GM081348 grant and the WVU Research Corporation)

Topics: Poster Session Abstracts
Publisher: Association of Biomolecular Resource Facilities
OAI identifier: oai:pubmedcentral.nih.gov:3186542
Provided by: PubMed Central
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