Vascular endothelial growth factor gene delivery by magnetic DNA nanospheres ameliorates limb ischemia in rabbits

Background. Critical limb ischemia often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote arteriogenesis and angiogenesis in animal models of limb ischemia. However, most of the studies used a nonspecific targeting system. Materials and methods. Magnetic DNA nanospheres containing expression plasmids encoding VEGF were synthesized, and their morphology, magnetropism, and stability were analyzed. The magnetic DNA nanospheres were administrated via an artery into a rabbit limb ischemia model. The expression of VEGF and vascularization were examined by immunohistochemistry. The angiography was taken to evaluate arteriogenesis. Results. Magnetic DNA nanospheres were very stable and showed a high magnetropism. Gene delivery of such nanospheres via artery under a magnetic field led to the overexpression of VEGF in situ. The capillary density and capillary to muscle fiber ratio were doubled compared with those of the control animals. The arteriogenesis also was promoted in VEGF gene therapy group compared with controls but at later interval than capillary angiogenesis. Conclusions. Our results suggest that intra-arterial VEGF gene delivery by magnetic DNA nanosphere promotes angiogenesis and arteriogenesis and presents a potent therapeutic strategy for critical limb ischemia. (C) 2005 Elsevier Inc. All rights reserved.