Injectable Carbon Nanotube-Functionalized Hydrogel for miRNA Delivery

摘要 microRNA（miRNAs）已被证实可促进心肌梗死后的心脏再生。然而，在这方面， 目前的miRNA递送方法，如病毒载体或脂质制剂，存在安全性问题， 广泛使用。我们开发了一种可注射的碳功能化热响应水凝胶 纳米管（RTG-CNT）用于递送miRNA。RTG-CNT水凝胶从液体-溶液转变为 在达到体温后不久，使用凝胶基质， 通过稳定的凝胶miRNA定位。此外，这种水凝胶具有改善的短期（8周）生物相容性 与病毒和脂质方法相比，它促进的miRNA表达是脂质制剂的两倍。 在这项研究中，我们提出测试的假设，我们的新型RTG-CNT水凝胶是远远优于上级 通过增加生物相容性、靶向递送和更高的生物相容性， 与病毒和脂质方法相比，miRNA表达。我们将用一个 1）量化生物相容性和改善的程度， 我们的RTG-CNT-miRNA递送系统在脂质体和病毒载体方法上的定位，2）测量 与脂质体相比，RTG-CNT水凝胶作为促再生miRNA递送系统的效率提高， 小鼠MI模型中的病毒载体递送，和3）确定RTG-CNT水凝胶递送 抗纤维化的miRNA，以进一步改善小鼠MI模型中的心肌结构和拯救功能。我们 我相信RTG-CNT水凝胶将提供一种生物相容性更好、效率更高的miRNA递送系统 比传统的方法，这可以实际地转化为临床应用。

ABSTRACT microRNAs (miRNAs) have been proven to promote cardiac regeneration after myocardial infarction. However, current miRNA delivery methods, such as viral vectors or lipid formulations, present safety concerns for widespread use. We have developed an injectable thermo-responsive hydrogel functionalized with carbon nanotubes (RTG-CNT) for the delivery of miRNAs. The RTG-CNT hydrogel transitions from a liquid-solution to a gel-based matrix shortly after reaching body temperature allowing for a liquid-based delivery rapidly followed by a stable-gel miRNA localization. Moreover, this hydrogel has improved short-term (8-week) biocompatibility compared to viral and lipid approaches and it promotes two-fold more miRNA expression than lipid formulations. In this investigation, we propose to test the hypothesis that our novel RTG-CNT hydrogel is far superior delivery model of miRNAs to the heart, through increased biocompatibility, targeted delivery and higher miRNA expression when compared to viral and lipid approaches. We will address our hypothesis with a combination of cell biology and bioengineering by 1) Quantify the biocompatibility and the magnitude of improved localization of our RTG-CNT-miRNA delivery system over liposomal and viral vectors approaches, 2) Measure the improved efficiency of the RTG-CNT hydrogel as pro-regenerative miRNA delivery system vs. liposomal and viral vector deliveries in a mouse MI model and 3) Determine the potential of the RTG-CNT hydrogel to deliver anti-fibrotic miRNAs to further improve myocardial structure and rescue function in a mouse MI model. We believe that the RTG-CNT hydrogel will offer a more biocompatible and far more efficient miRNA delivery system than traditional approaches, that can be realistically translated into clinical applications.