H(2)O(2)-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs.
H(2)O(2)-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs.
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H2O2响应性VEGF/NGF基因共传递纳米系统在缺血后肢实现稳定血管化
DOI：
10.1186/s12951-022-01328-6
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发表时间：
2022-03-19
影响因子：
10.2
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Chen Y;Chen Z;Duan J;Gui L;Li H;Liang X;Tian X;Liu K;Li Y;Yang J
外周血管疾病(PVD)是动脉粥样硬化的常见临床表现。血管内皮生长因子(VEGF)基因治疗PVD是一种很有前途的治疗方法。然而，由于单基因治疗的局限性和较高的H_2O_2病理微环境，血管内皮生长因子的基因治疗效果并不理想，其临床应用受到限制。近年来，神经因子和血管因子在血管生成中的协同作用引起了人们的关注。本研究以过氧化氢响应型6S-PLGA-Po-PEG为载体，制备了血管内皮生长因子和神经生长因子基因共传递纳米粒(VEGF/NGF-NPs)。6S-PLGA-Po-PEG能与H_2O_2通过过氧草酸键发生特异性反应。血管内皮生长因子/神经生长因子纳米粒在细胞和后肢缺血小鼠模型中的血管生成作用已被评估。结果表明，VEGF/NGF-NPs同时促进了VEGF和NGF的共表达，清除了过量的过氧化氢，加强了SH-SY5Y与HUVECs的反应，最终增强了HUVECs的迁移、管状形成、增殖和抗H2O2损伤能力。血管内皮细胞生长因子/神经生长因子纳米粒可恢复血供，促进血管内皮生长因子、神经生长因子、内皮型一氧化氮合酶和一氧化氮的表达，增加周细胞的血管覆盖率。血管内皮生长因子/神经生长因子纳米粒的治疗作用可能与血管内皮生长因子/eNOS/NO通路有关。总之，VEGF/NGF-NPs在实现基因共传递的同时消除了过量的过氧化氢，并促进了稳定的血管生成。应用血管内皮细胞生长因子/神经生长因子纳米粒治疗PVD是一种很有前途的方法。网上版载有补充材料，可在10.1186/s12951-022-01328-6查阅。
Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs. The online version contains supplementary material available at 10.1186/s12951-022-01328-6.
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影响因子：
1.6
作者：
Park JC;Chang IB;Ahn JH;Kim JH;Song JH;Moon SM;Park YH
通讯作者：
Park YH
DOI：
10.1073/pnas.1814874116
发表时间：
2019-04-09
影响因子：
11.1
作者：
Liu, Chang;Ge, Hui-Min;Yan, Biao
通讯作者：
Yan, Biao
DOI：
10.1016/j.ijom.2015.06.016
发表时间：
2015-12-01
影响因子：
2.4
作者：
Guang, M.;Yao, Y.;Gong, P.
通讯作者：
Gong, P.
影响因子：
2
作者：
Kastrup, Jens
通讯作者：
Kastrup, Jens
影响因子：
37.8
作者：
Emanueli, C;Salis, MB;Mededdu, P
通讯作者：
Mededdu, P