조훈성 (Massachusetts General Hospital, Harvard Medical School)

한빛사논문

조회2,576

Massachusetts General Hospital, Harvard Medical School

ACS Nano, February 1, 2013 | DOI: 10.1021/nn305962n Fluorochrome-Functionalized Nanoparticles for Imaging DNA in Biological Systems

Abstract

Hoonsung Cho^†, David Alcantara^‡, Hushan Yuan^†, Rahul A. Sheth^§, Howard H. Chen^⊥ , Peng Huang^∥ , Sean B. Andersson^{∥ ¶}, David E. Sosnovik , Umar Mahmood^†§, and Lee Josephson^†⊥*

^†Center for Translational Nuclear Medicine and Molecular Imaging, ^§Division of Nuclear Medicine & Molecular Imaging, Department of Radiology, and ^⊥Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, United States
^‡ Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Spain
^∥Department of Mechanical Engineering and ^¶Division of Systems Engineering,Boston University, Massachusetts 02215, United States

^*Address correspondence to Lee Josephson
Abstract
Attaching DNA binding fluorochromes to nanoparticles (NPs) provides a way of obtaining NPs that bind to DNA through fluorochrome mediated interactions. To obtain a nanoparticle (NP) that bound to the DNA in biological systems, we attached the DNA binding fluorochrome, TO-PRO 1 (TO), to the surface of the Feraheme (FH) NP, to obtain a fluorochrome-functionalized NP denoted TO-FH. When reacted with DNA in vitro, TO-FH formed microaggregates that were characterized by fluorescence, light scattering, and T2 changes. The formation of DNA/TO-FH microaggregates was also characterized by AFM, with microaggregates exhibiting a median size of 200 nm, and consisting of DNA and multiple TO-FH NPs whose individual diameters were only 25 - 35 nm. TO-FH failed to bind normal cells in culture, but treatment with chemotherapeutic agents or detergents yielded necrotic cells that bound TO-FH and vital fluorochromes similarly. The uptake of TO-FH by HT-29 xenografts (treated with 5-FU and oxaliplatin) was evident by surface fluorescence and MRI. Attaching multiple DNA binding fluorochromes to magnetic nanoparticles provides a way of generating DNA binding NPs that can be used to detect DNA detection by microaggregate formation in vitro, for imaging the DNA of necrotic cells in culture, and for imaging the DNA of a tumor treated with a chemotherapeutic agent. Fluorochrome functionalized NPs are a multimodal (magnetic and fluorescent), highly multivalent (n ≈ 10 fluorochromes/NP) nanomaterials useful for imaging the DNA of biological systems.

Keywords: DNA; imaging; nanoparticle; fluorochrome; biosensing

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형식Research article
게재일2013년 02월 (BRIC 등록일 )
연구진국외 연구진
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