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Letter

Covalently Linked Au Nanoparticles to a Viral Vector: Potential for Combined Photothermal and Gene Cancer Therapy

Supporting Info

Maaike Everts,^† Vaibhav Saini,^†^‡ Jennifer L. Leddon,^† Robbert J. Kok,^§ Mariam Stoff-Khalili,^† Meredith A. Preuss,^† C. Leigh Millican, Guy Perkins, Joshua M. Brown, Hitesh Bagaria,^# David E. Nikles,^# Duane T. Johnson,^# Vladimir P. Zharov,⁺ and David T. Curiel*^†

Division of Human Gene Therapy, Departments of Medicine, Surgery, Pathology and the Gene Therapy Center, High-Resolution Imaging Facility, and Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, Department of Pharmacokinetics and Drug Delivery, University Center for Pharmacy, Groningen University Institute for Drug Exploration (GUIDE), 9713 AV Groningen, The Netherlands, National Center for Microscopy and Imaging Research, Center for Research on Biological Structure School of Medicine, University of California, San Diego, California 92093, Center for Materials for Information Technology (MINT), University of Alabama, Tuscaloosa, Alabama 35487, and Philips Classic Laser Laboratories, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

Nano Lett., 2006, 6 (4), pp 587–591

DOI: 10.1021/nl0500555

Publication Date (Web): March 15, 2006

Abstract

Hyperthermia can be produced by near-infrared laser irradiation of gold nanoparticles present in tumors and thus induce tumor cell killing via a bystander effect. To be clinically relevant, however, several problems still need to be resolved. In particular, selective delivery and physical targeting of gold nanoparticles to tumor cells are necessary to improve therapeutic selectivity. Considerable progress has been made with respect to retargeting adenoviral vectors for cancer gene therapy. We therefore hypothesized that covalent coupling of gold nanoparticles to retargeted adenoviral vectors would allow selective delivery of the nanoparticles to tumor cells, thus feasibilizing hyperthermia and gene therapy as a combinatorial therapeutic approach. For this, sulfo-N-hydroxysuccinimide labeled gold nanoparticles were reacted to adenoviral vectors encoding a luciferase reporter gene driven by the cytomegalovirus promoter (AdCMVLuc). We herein demonstrate that covalent coupling could be achieved, while retaining virus infectivity and ability to retarget tumor-associated antigens. These results indicate the possibility of using adenoviral vectors as carriers for gold nanoparticles.

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