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Iron Oxide Nanoclusters as In Vitro Biosensors of Proteolytic Activity

We demonstrate a flexible, tunable scheme for synthesizing multifunctional, ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and its application to the area of magnetic relaxation switches. USPIO cores (10nm) were functionalized with a poly(propylene sulfide)-bl-poly(ethylene glycol) (PPS-PEG) copolymer, yielding ~40nm micelles. PPS-PEG-ssDNA conjugates and fluorophore-conjugated PPS-PEG are incorporated into the micelle synthesis process, yielding ssDNA-coated magnetofluorescent particles. To form magnetic relaxation switches, we generated USPIO populations that display complementary ssDNA sequences. Mixing of complementary USPIOs leads to clustering, resulting in a significant increase in R2 magnetic relaxation. Treatment of the DNA-crosslinked USPIO clusters with restriction enzymes specific for the crosslinking sequence results in an irreversible return of R2 relaxation to baseline levels. The constructs demonstrate their utility as nanoscale sensors of restriction enzyme activity. The presented functionalization scheme can be extended to the generation of biosensors for other sources of proteolytic activity, for diagnostics and imaging applications for cancer and atherosclerosis.

Identiferoai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12082009-144324
Date21 December 2009
CreatorsYu, Shann Claybourne Say
ContributorsHak-Joon Sung, Todd D. Giorgio
PublisherVANDERBILT
Source SetsVanderbilt University Theses
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.library.vanderbilt.edu/available/etd-12082009-144324/
Rightsunrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.

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