Studies have shown that the use of proangiogenic genes can improve the prognosis of
ischemic stroke by promoting angiogenesis at the injury site. For example, within this study,
hypoxia-inducible factor 1-α (HIF-1α) has exhibited an angiogenic effect. Our previous study reported a more stable HIF-1α mutant form (HIF-1α-AA), which was transfected into mesenchymal stem cells to provide
neuroprotective effects against
ischemic stroke. The safety of nonviral gene vectors has attracted researchers' attention. This study encapsulated the HIF-1α-AA plasmid
DNA into a newly synthesized effective nonviral gene vector, a hyperbranched cationic
amylopectin derivative (
DMAPA-Amyp) nanocarrier. In addition, a targeting strategy was applied to select the RGD
peptides and bind to the designed nanocarrier as a molecule targeting endothelial cells. The targeting strategy is used to directly deliver the nanocarriers to the vascular endothelial cells of the brain peri-
infarct site. This study emphasizes the targeting ability of nanocarrier and its
therapeutic effect on
cerebral ischemia. The results showed that RGD-
DMAPA-Amyp had good biocompatibility and a high cell uptake rate, indicating that it is a safe nonviral gene vector that can be endocytosed by human cells. In rat models of
ischemic stroke, compared with the nontargeted nanocarrier group, more RGD-
DMAPA-Amyp nanoparticles aggregated in vascular endothelial cells of the peri-
infarct region and significantly improved the recovery of neurological function. It is indicated that the RGD-modified nanomedicine promotes the recovery of nerve function more efficiently. Further study on the mechanism of RGD-
DMAPA-Amyp/HIF-1α-AA in the treatment of
cerebral ischemia displayed potential to significantly promote the formation of new blood vessels in vivo. Our findings suggest that the RGD-modified nonviral gene vector containing HIF-1α-AA appears to be a safe and promising therapeutic strategy for
ischemic stroke gene therapy.