Poly(methylidene malonate 2.1.2) nanoparticles: a biocompatible polymer that enhances peri-adventitial adenoviral gene delivery.
Vascular gene therapy is currently limited by low and transient levels of gene transfection. The objectives of this study were to determine whether peri-adventitial delivery of adenovirus coupled to nanoparticles could improve transfection efficiency and duration. Adenovirus was absorbed to the surface of nanoparticles that were made from poly(methylidene malonate)2.1.2 (PMM2.1.2). These complexes were found to have good adhesive properties to both cultured vascular smooth muscle cells and to the luminal and adventitial layers of excised rabbit carotid arteries. Adenovirus encoding to beta-galactosidase coupled to PMM2.1.2 nanoparticles or adenovirus alone were delivered locally to the adventitia of rabbit carotid arteries. Transfection rate was assessed histologically by the percentage of beta-galactosidase positive cells in the vessel wall at 1 and at 2 weeks. There was significantly higher transfection rate when adenovirus was complexed with nanoparticles as compared to free adenovirus (At 1 week: 10+/-3.9% beta-gal positive cells vs. 2.4+/-0.3% and at 2 weeks: 4.3+/-4.1% vs. 0%, P<0.005 for all). This difference was present in both the medial and adventitial layers. In conclusion, adenoviral mediated gene therapy was significantly enhanced by adsorbing the virus to PMM2.1.2 nanoparticles. This delivery method may be a good therapeutic strategy for the treatment of various vascular diseases.
Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, 4 Taddle Creek Road, Room 407, Toronto, Ont., Canada M5S 3G9.
Beiping
B
Qiang
Amit
A
Segev
Isabelle
I
Beliard
Nafiseh
N
Nili
Bradley H
BH
Strauss
Michael V
MV
Sefton
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001672:Biocompatible Materials; D002478:Cells, Cultured; D015316:Genetic Therapy / Q000379:methods*; D008314:Malonates; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D011095:Polyethylenes; D011817:Rabbits; D014014:Tissue Adhesives; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D001672:Biocompatible Materials; D008314:Malonates; D011095:Polyethylenes; D014014:Tissue Adhesives; C091414:poly(methylidene malonate) 2.1.2; D001616:beta-Galactosidase