An adenoviral platform for selective self-assembly and targeted delivery of nanoparticles.
Metallic nanoparticles (NPs) can be used for the diagnosis, imaging, and therapy of tumors and cardiovascular disease. However, targeted delivery of NPs to specific cells remains a major limitation for clinical realization of these potential treatment options. Herein, a novel strategy for the specific coupling of NPs to a targeted adenoviral (Ad) platform to deliver NPs to specific cells is defined. Genetic manipulation of the gene-therapy vector is combined with a specific chemical coupling strategy. In particular, a high-affinity interaction between a sequence of six-histidine amino acid residues genetically incorporated into Ad capsid proteins and nickel(II) nitrilotriacetic acid on the surface of gold NPs is employed. The selective self-assembly of gold NPs and Ad vectors into multifunctional platforms does not negatively affect the targeting of Ad to specific cells. This opens the possibility of using Ad vectors for targeted NP delivery, thereby providing a new type of combinatorial approach for the treatment of diseases that involves both nanotechnology and gene therapy.
Saini
Vaibhav
V
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Martyshkin
Dmitri V
DV
Mirov
Sergei B
SB
Perez
Alex
A
Perkins
Guy
G
Ellisman
Mark H
MH
Towner
Victoria D
VD
Wu
Hongju
H
Pereboeva
Larisa
L
Borovjagin
Anton
A
Curiel
David T
DT
Everts
Maaike
M
D000256:Adenoviridae / Q000235:genetics*; D036022:Capsid Proteins / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006046:Gold; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D013054:Spectrophotometry, Atomic
D036022:Capsid Proteins; D002272:Carcinoembryonic Antigen; D006046:Gold