Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair.
Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair.
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DOI：
10.1021/nn5020787
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发表时间：
2014-08-26
期刊：
影响因子：
17.1
通讯作者：
Khademhosseini, Ali
中科院分区：
文献类型：
--
作者：
Paul, Arghya;Hasan, Anwarul;Al Kindi, Hamood;Gaharwar, Akhilesh K.;Rao, Vijayaraghava T. S.;Nikkhah, Mehdi;Shin, Su Ryon;Krafft, Dorothee;Dokmeci, Mehmet R.;Shum-Tim, Dominique;Khademhosseini, Ali
本研究的目的是开发一种可注射的生物相容性水凝胶，该水凝胶可以有效地递送氧化石墨烯（GO）和血管内皮生长因子-165 （VEGF）促血管生成基因的纳米复合物，用于心肌治疗。在这项研究中，利用聚乙烯亚胺（PEI）功能化氧化石墨烯纳米片（fGO）与DNAVEGF配合，配制了一种高效的非病毒基因传递系统，并将其掺入低模量甲基丙烯酸明胶（GelMA）水凝胶中，以促进可控和局部基因治疗。假设fGOVEGF/GelMA纳米复合水凝胶可以有效转染心肌组织并诱导良好的治疗效果，而不引起细胞毒性作用。为了验证这一假设，我们建立了急性心肌梗死大鼠模型，并将治疗性水凝胶注射到梗死周围区域的心肌内。体外转染的心肌细胞分泌的VEGF对内皮细胞表现出深刻的有丝分裂活性。与未治疗的sham、GelMA和DNAVEGF/GelMA组相比，fGOVEGF/GelMA组梗死心脏注射梗死周围区心肌毛细血管密度显著增加，瘢痕面积减少。此外，注射后14天，fGOVEGF/GelMA组心脏超声心动图表现明显高于其他组（p < 0.05, n = 7）。此外，氧化石墨烯/GelMA组与非氧化石墨烯组在注射部位的血清细胞因子水平和基于定量PCR的炎症microRNA （miRNA）标记物表达方面没有显著差异。总的来说，目前的研究结果表明，利用氧化石墨烯和DNA的非病毒杂交复合物，建立一种基于水凝胶的缺血性心脏病基因治疗系统是可行的。
The objective of this study was to develop an injectable and biocompatible hydrogel which can efficiently deliver a nanocomplex of graphene oxide (GO) and vascular endothelial growth factor-165 (VEGF) pro-angiogenic gene for myocardial therapy. For the study, an efficient nonviral gene delivery system using polyethylenimine (PEI) functionalized GO nanosheets (fGO) complexed with DNAVEGF was formulated and incorporated in the low-modulus methacrylated gelatin (GelMA) hydrogel to promote controlled and localized gene therapy. It was hypothesized that the fGOVEGF/GelMA nanocomposite hydrogels can efficiently transfect myocardial tissues and induce favorable therapeutic effects without invoking cytotoxic effects. To evaluate this hypothesis, a rat model with acute myocardial infarction was used, and the therapeutic hydrogels were injected intramyocardially in the peri-infarct regions. The secreted VEGF from in vitro transfected cardiomyocytes demonstrated profound mitotic activities on endothelial cells. A significant increase in myocardial capillary density at the injected peri-infarct region and reduction in scar area were noted in the infarcted hearts with fGOVEGF/GelMA treatment compared to infarcted hearts treated with untreated sham, GelMA and DNAVEGF/GelMA groups. Furthermore, the fGOVEGF/GelMA group showed significantly higher (p < 0.05, n = 7) cardiac performance in echocardiography compared to other groups, 14 days postinjection. In addition, no significant differences were noticed between GO/GelMA and non-GO groups in the serum cytokine levels and quantitative PCR based inflammatory microRNA (miRNA) marker expressions at the injected sites. Collectively, the current findings suggest the feasibility of a combined hydrogel-based gene therapy system for ischemic heart diseases using nonviral hybrid complex of fGO and DNA.
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影响因子：
14
作者：
Lin, Ruei-Zeng;Chen, Ying-Chieh;Moreno-Luna, Rafael;Khademhosseini, Ali;Melero-Martin, Juan M.
通讯作者：
Melero-Martin, Juan M.
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
41.2
作者：
Kong, HJ;Liu, JD;Mooney, DJ
通讯作者：
Mooney, DJ
影响因子：
56.9
作者：
LANGER, R;VACANTI, JP
通讯作者：
VACANTI, JP
影响因子：
10
作者：
Mihaila, Silvia M.;Gaharwar, Akhilesh K.;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali