title: Covalently linked Au nanoparticles to a viral vector: potential for combined photothermal and gene cancer therapy.
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.
authors.affiliation: Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, University of Alabama, Birmingham, Alabama 35294, USA.
authors.forename: Maaike
authors.initials: M
authors.lastname: Everts
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Saini
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Leddon
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Kok
authors.forename: Mariam
authors.initials: M
authors.lastname: Stoff-Khalili
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Preuss
authors.forename: C Leigh
authors.initials: CL
authors.lastname: Millican
authors.forename: Guy
authors.initials: G
authors.lastname: Perkins
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Brown
authors.forename: Hitesh
authors.initials: H
authors.lastname: Bagaria
authors.forename: David E
authors.initials: DE
authors.lastname: Nikles
authors.forename: Duane T
authors.initials: DT
authors.lastname: Johnson
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
mesh_terms: D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics*; D001665:Binding Sites; D002470:Cell Survival / Q000528:radiation effects; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008027:Light; D043942:Nanotubes / Q000737:chemistry; D010789:Phototherapy / Q000379:methods*
chemical_list: D006046:Gold