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A fluorinated low-molecular-weight PEI/HIF-1α shRNA polyplex system for hemangioma therapy
Biomaterials Science ( IF 6.6 ) Pub Date : 2020-03-31 , DOI: 10.1039/d0bm00171f
Xiaoshuang Guo 1, 2, 3, 4, 5 , Zihan Yuan 1, 2, 3, 4, 5 , Yang Xu 1, 2, 3, 4, 5 , Minyan Wei 1, 2, 3, 4, 5 , Zhiwei Fang 1, 2, 3, 4, 5 , Wei-En Yuan 1, 2, 3, 4, 5
Affiliation  

Hemangioma, one of the most common angiogenic diseases in infants and children, is characterized by the abnormal and aggressive proliferation of vascular endothelial cells. 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 owing to the lack of safe carriers. In this study, we showed for the first time that RNAi technology targeting HIF-1α (hypoxia-inducible factor-1 alpha) could benefit hemangioma therapy effectively. Heptafluorobutyric anhydride (HFAA) was used to modify low-molecular-weight PEI (PEI1.8k), and a novel fluorinated polycation carrier named fluorinated PEI (FPEI) was synthesized. Furthermore, HIF-1α-shRNA-pDNA was condensed by FPEI to fabricate FPEI polyplexes. Compared with PEI25k polyplexes, which are usually 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.

中文翻译:

氟化低分子量PEI /HIF-1αshRNA复合系统用于血管瘤治疗

血管瘤是婴儿和儿童中最常见的血管生成性疾病之一,其特征在于血管内皮细胞的异常和侵袭性增殖。RNA干扰等先进的治疗策略可以在翻译水平上抑制靶蛋白的表达,但由于缺乏安全的载体,它们很少用于血管瘤的治疗。在这项研究中,我们首次证明了针对HIF-1α(低氧诱导因子-1α)的RNAi技术可以有效地使血管瘤治疗受益。用七氟丁酸酐(HFAA)对低分子量PEI(PEI1.8k)进行改性,合成了一种新型的氟化聚阳离子载体,称为氟化PEI(FPEI)。此外,HFP-1α-shRNA-pDNA通过FPEI进行缩合以制备FPEI多链体。与PEI25k复合物相比,体外体内。此外,我们证实FPEI复合物可以有效地抑制体内新毛细血管的形成和肿瘤的生长,这可能为将来的临床血管瘤治疗提供实用的策略。
更新日期:2020-04-24
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