Covalent Organic Framework (COF): A Drug and Carrier to Attenuate Retinal Ganglion Cells Death in an Acute Glaucoma Mouse Model.
Covalent Organic Framework (COF): A Drug and Carrier to Attenuate Retinal Ganglion Cells Death in an Acute Glaucoma Mouse Model.
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目的：我们的目的是研究共价有机框架（COF）纳米颗粒在青光眼局部治疗中的应用，既可以作为保护视网膜神经节细胞（RGCs）的手段，也可以作为单次玻璃体内注射雷帕霉素延迟释放的载体。方法：制备水分散COF，构建基于COF的雷帕霉素纳米释放平台（COF- rapa）。将C57BL/6J小鼠随机分为4组，分别玻璃体内注射生理盐水1.5µL、COF （0.67 ng/µL）、雷帕霉素（300µM）、COF- rapa （0.67 ng/µL-300µM）。建立模拟高眼压（IOP）致青光眼视网膜损伤的缺血-再灌注（I/R）模型。用荧光金标记RGCs和视网膜电图评价视网膜功能。对视网膜进行免疫组化和Western blotting分析。结果：COF纳米颗粒在体内和体外均获得了良好的递送效果。注射COF 6周后，rgc数量未受影响。此外，rbpms阳性RGCs、gfap阳性星形胶质细胞和iba1阳性小胶质细胞的数量与正常对照组没有差异。与NS对照相比，COF能有效降低视网膜I/R损伤后RGCs的死亡，改善光传导功能，减轻小胶质细胞的过度激活。在6周内，通过单次玻璃体内注射COF-Rapa，可以抑制哺乳动物视网膜中雷帕霉素复合物1 （mTORC1）信号通路的靶点。与单一给药相比，COF- rapa可显著降低视网膜I/R损伤后的炎症反应。结论：COF既可作为RGC保护剂，又可作为雷帕霉素缓释载体。这项研究可能会导致新的RGC保护剂和药物递送技术的发展，以及基于cof的多功能青光眼视网膜病变生物材料的创造。
Purpose: We aim to investigate the use of covalent organic framework (COF) nanoparticles in the local treatment of glaucoma, both as a means of protecting retinal ganglion cells (RGCs), and as a carrier for delayed release of the medication rapamycin following a single intravitreal injection. Methods: a water-dispersible COF, and a COF-based nanoplatform for rapamycin release (COF-Rapa) was constructed. C57BL/6J mice were randomly divided into four groups: intravitreal injection of 1.5 µL normal saline (NS), COF (0.67 ng/µL), rapamycin (300 µM) or COF-Rapa (0.67 ng/µL-300 µM), respectively. The ischemia–reperfusion (I/R) model was established to mimic high intraocular pressure (IOP)-induced retinal injury in glaucoma. Labeling of RGCs by Fluoro-Gold and retinal electroretinogram were used to evaluate retinal function. Immunohistochemistry and Western blotting analyses of retinas were performed. Results: COF nanoparticles were delivered in vitro and in vivo. Six weeks after the COF injection, the number of RGCs was unaffected. In addition, the number of RBPMS-positive RGCs, GFAP-positive astrocytes and Iba1-positive microglia did not differ from the normal control. COF could effectively reduce RGCs death, improve phototransduction function and alleviate the overactivation of microglia compared to NS control after retinal I/R injury. Within six weeks, the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in the retinas could be inhibited by a single intravitreal injection of COF-Rapa. Compared with single COF administration, COF-Rapa significantly reduced the inflammatory reaction after retinal I/R injury. Conclusions: COF may act as both an RGC protection agent and a carrier for prolonged rapamycin release. This research may lead to the development of novel RGC protection agents and drug delivery techniques, as well as the creation of multifunctional COF-based biomaterials for glaucoma retinopathy.
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影响因子：
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作者：
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DOI：
10.1073/pnas.2014213117
发表时间：
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