Adenoviral gene delivery to solid tumors by recombinant silk-elastinlike protein polymers.
OBJECTIVE
The purpose of this study was to investigate the potential of silk-elastinlike protein polymers (SELPs) in controlling the release rate of adenoviruses in vitro and in vivo while preserving their bioactivity.


METHODS
A hydrogel system composed of SELP/adenovirus mixture was prepared. The release of the adenovirus particles from the hydrogels was quantified by Real Time-PCR and the bioactivity of the released viruses was evaluated using confocal microscopy and beta-galactosidase assay. To demonstrate the ability of SELP in entrapping virus cargo and releasing it over a prolonged period of time in vivo, a SELP/adenovirus mixture was prepared and injected directly into xenograft tumor models of breast and head and neck cancer in mice. At various time points mice were sacrificed, tumors dissected, and tissue sections studied under confocal microscope.


RESULTS
In vitro studies demonstrated that SELP hydrogels release viruses over a period of 4 weeks while preserving their bioactivity. After intratumoral injection, a prolonged and localized expression of adenoviruses was observed.


CONCLUSIONS
These results suggest the potential of SELPs in local adenoviral delivery to solid tumors as an alternative approach to intratumoral virus infusion.
Hatefi
A
A
Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201-1075, USA.
Cappello
J
J
Ghandehari
H
H
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D020100:Hydrogels; D007763:Lac Operon; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011991:Receptors, Virus / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D001704:Biopolymers; D020100:Hydrogels; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C085301:adenovirus receptor; D049452:Green Fluorescent Proteins