| Hemangioma,characterized by the abnormal and aggressive proliferation of vascular endothelial cells,is one of the most common angiogenic diseases in infants and children.At present,the treatment methods for hemangioma mainly include drug therapy,laser therapy and operative management.However,these treatments cannot cure hemangiomas directly,and sometimes they can cause various local and systemic side effects.Advanced therapeutic strategies like RNA interference can inhibit the expression of target proteins at the translational level,but they are rarely used in hemangioma treatment for lack of safe carriers.HIF-1a is an important transcription factor that regulates cellular responses to hypoxia,and it plays an important role in the occurrence and growth of tumors.In this study,we showed for the first time that RNAi technology targeting HIF-1α could benefit hemangioma therapy effectively.We designed a novel polycationic carrier with low cytotoxicity,high serum stability,endocytosis efficiency,transfection efficiency,and silencing efficiency to achieve the efficient delivery of HIF-1α-sh RNA p DNA,thereby achieving effective treatment of hemangiomas.Heptafluorobutyric anhydride(HFAA)was used to modify low-molecular-weight PEI(PEI 1.8 k Da),and a novel fluorinated polycation carrier named fluorinated PEI(FPEI)was synthesized.Furthermore,HIF-1α-sh RNA p DNA was condensed by FPEI to fabricate FPEI polyplexes.When these polyplexes were delivered into cells,they could inhibit the expression of target proteins,and could thus inhibit the tumor growth.Compared with PEI 25 k Da polyplexes,the gold standard used in gene delivery,FPEI polyplexes showed lower cytotoxicity and higher serum stability,transfection efficiency and gene silencing efficiency both in vitro and in vivo.In addition,we confirmed that FPEI polyplexes could efficiently inhibit the formation of new capillaries and tumor growth in vivo,which may provide a practicable strategy for clinical hemangioma treatment in the future. |
