Biomedical Applications of Gold Nanoparticles Functionalized Using Hetero-Bifunctional Poly(ethylene glycol) Spacer
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Biomedical Applications of Gold Nanoparticles Functionalized Using Hetero-Bifunctional Poly(ethylene glycol) Spacer Wei Fu1, Dinesh Shenoy2, Jane Li3, Curtis Crasto3, Graham Jones3, Charles Dimarzio4, Srinivas Sridhar1, and Mansoor Amiji2 1
Department of Physics, 2Department of Pharmaceutical Sciences, 3Department of Chemistry and Chemical Biology, 4Department of Electrical and Computer Engineering and the Keck Microscope Facility, Northeastern University, Boston, MA 02115
Abstract To increase the targeting potential, circulation time, and the flexibility of surface-attached biomedically-relevant ligands on gold nanoparticles, hetero-bifunctional poly(ethylene glycol) (PEG, MW 1,500) was synthesized having a thiol group on one terminus and a reactive functional group on the other. Coumarin, a model fluorescent dye, was conjugated to the PEG spacer and gold nanoparticles were modified with coumarin-PEG-thiol. Surface attachment of coumarin through the PEG spacer decreases the fluorescence quenching effect of gold nanoparticles. The results of cellular cytotoxicity and fluorescence confocal analyses showed that the PEG spacer modified nanoparticles were essentially non-toxic and could be efficiently internalized in the cells within one hour of incubation. Introduction Nanotechnology offers unique approaches to probe and control a variety of biological and medical processes that occur at nanometer length scales, and is expected to have a revolutionary impact on biology [1] and medicine [2]. Among the approaches for exploiting nanotechnology in medicine, nanoparticles offer some unique advantages as sensing, image enhancement, and delivery agents [3,4]. Several varieties of nanoparticles with biomedical relevance are available including, polymeric nanoparticles, metal nanoparticles, liposomes, micelles, quantum dots, dendrimers, and nanoassemblies. To further the application of nanoparticles in disease diagnosis and therapy, it is important that the systems are biocompatible and capable of being functionalized for recognition of specific target sites in the body after systemic administration. Nanoparticles based on gold chemistry have attracted significant research and practical attention recently. They are versatile agents with a variety of biomedical applications including use in highly sensitive diagnostic assays [5], thermal ablation and radiotherapy enhancement [6,7], as well as drug and gene delivery [8]. For instance, antibody-modified gold nanoparticles when used for detection of prostate specific antigen, had an almost a million-fold higher sensitivity that conventional ELISA-based assay [9]. Near-infrared radiation absorbing gold-silica nanoshells have been prepared and evaluated for thermal ablation of tumors after systemic administration [6]. For biomedical applications, surface functionalization of gold nanoparticles is essential in order to target them to specific disease areas and allow them to selectively interact with cells or biomolecules. Surface conjugation of antibodies and other targetin
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