Covalently linked Au nanoparticles to a viral vector: potential for combined photothermal and gene cancer therapy.
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.
Everts
Maaike
M
Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, University of Alabama, Birmingham, Alabama 35294, USA.
Saini
Vaibhav
V
Leddon
Jennifer L
JL
Kok
Robbert J
RJ
Stoff-Khalili
Mariam
M
Preuss
Meredith A
MA
Millican
C Leigh
CL
Perkins
Guy
G
Brown
Joshua M
JM
Bagaria
Hitesh
H
Nikles
David E
DE
Johnson
Duane T
DT
Zharov
Vladimir P
VP
Curiel
David T
DT
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*
D006046:Gold