Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2007, Article ID 76514, 9 pages doi:10.1155/2007/76514 Research Article Imaging GABA c Receptors with Ligand-Conjugated Quantum Dots Ian D. Tomlinson, 1 H´ el` ene A. Gussin, 2 Deborah M. Little, 2, 3 Michael R. Warnement, 1 Haohua Qian, 2 David R. Pepperberg, 2 and Sandra J. Rosenthal 1 1 Department of Chemistry, Vanderbilt University, Station B 311822, Nashville, TN 37235, USA 2 Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA 3 Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL 60612, USA Correspondence should be addressed to Sandra J. Rosenthal, sandra.j.rosenthal@vanderbilt.edu Received 14 May 2007; Revised 30 August 2007; Accepted 21 December 2007 Recommended by Marek Osinski We report a methodology for labeling the GABA c receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABA C receptors heterologously expressed in Xenopus laevis oocytes. Copyright © 2007 Ian D. Tomlinson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. INTRODUCTION Quantum dots (qdots) are nanometer-sized semiconductor crystals that have unique physical properties that differ from bulk material. The fluorescent properties of qdots have been widely described, and numerous applications based upon these fluorescent properties have been reported. In addition, previous studies have reported the properties of many varieties of qdots [1–8]. Of these, the most widely studied are cadmium selenide/zinc sulfide core-shell nanocrystals. These consist of a semiconductor core of cadmium selenide encapsulated in a multilayer shell of zinc sulfide doped with cadmium [9]. The shell passivates the surface of the core, and the band gap is wider than that of the core, enabling quantum confinement of an electron-hole pair generated in the core after photoexcitation. Ultimately, the electron hole pair recombines, resulting in a fluorescent emission of a lower- energy photon in the visible region of the spectrum [10]. The energy of the emitted photon is determined by the size of the quantum confinement (or the size of the qdot). Smaller qdots emit blue light and larger ones emit red light. Qdots have several advantages over conventional fluorescent dyes; these include increased photostability, increased brightness, quantum yields in excess of 80–90% [1, 9, 11], and a narrow emission spectrum (less than 30 nm full width at half- maximum in commercial products) [12–15]. Furthermore, their multivalent surfaces enable the attachment of more than one type of ligand or multiple copies of a ligand to a single qdot. Since their introduction into biology as imaging agents in 1998 [16, 17], qdots have increasingly found applications as fluorescent probes in biology. To be useful as fluorescent probes in biological systems, qdots must be soluble in water and commonly used buffers. Additionally, they must have colloidal stability and low nonspecific adsorption to cellular membranes. These properties have been achieved using a number of techniques, including encapsulation in micelles [18], silanization [19], encapsulation in amphiphilic polymers [20, 21], and encapsulation in proteins such as streptavidin [22]. To further reduce nonspecific adsorption to cellular membranes, a number of techniques may be used to modify the surface chemistry of qdots. For example, we have recently demonstrated that nonspecific binding can be significantly reduced by attaching polyethylene glycol chains (i.e., by PEGylating) qdots coated in an amphiphilic modified polyacrylic acid polymer (AMP) [23]. The length of the PEG chain and the PEG loading were demonstrated to be important in reducing nonspecific adsorption to cellular