Department of Ophthalmology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai, 200433, China.
J Nanobiotechnology. 2022 Apr 2;20(1):174. doi: 10.1186/s12951-022-01362-4.
Pathological retinal angiogenesis resulting from a variety of ocular diseases including oxygen induced retinopathy, diabetic retinopathy and ocular vein occlusion, is one of the major reasons for vision loss, yet the therapeutic option is limited. Multiple nanoparticles have been reported to alleviate angiogenic retinopathy. However, the adverse effect cannot be ignored due to the relatively large scale. Graphene quantum dots (GQDs) have shown potential in drug delivery and have been proved biocompatible. In this study, Graphene quantum dots are extensively investigated for their application in angiogenic retinopathy therapy.
We showed that GQDs were biocompatible nanomaterials in vitro and in vivo. The nanoparticles have a dose-dependent inhibitory effect on proliferation, migration, tube formation and sprouting of human umbilical vein endothelial cells (HUVECs). Further data show that GQDs could inhibit pathological retinal neovascularization in an oxygen-induced retinopathy (OIR) model. The data of RNA sequencing suggested that periostin is involved in this process. GQDs inhibit the expression of periostin via STAT3, and further regulated cell cycle-related protein levels through ERK pathway. The signaling pathway was conformed in vivo using OIR mouse model.
The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.
病理性视网膜血管生成是由多种眼病引起的,包括氧诱导的视网膜病变、糖尿病视网膜病变和眼静脉阻塞等,是导致视力丧失的主要原因之一,但治疗选择有限。已有多种纳米颗粒被报道可缓解血管生成性视网膜病变。然而,由于规模相对较大,其不良反应不容忽视。石墨烯量子点 (GQDs) 在药物输送方面显示出了潜力,并已被证明具有生物相容性。在这项研究中,广泛研究了 GQDs 在血管生成性视网膜病变治疗中的应用。
我们表明 GQDs 是体外和体内具有生物相容性的纳米材料。这些纳米颗粒对人脐静脉内皮细胞(HUVEC)的增殖、迁移、管形成和发芽具有剂量依赖性抑制作用。进一步的数据表明,GQDs 可以抑制氧诱导的视网膜病变(OIR)模型中的病理性视网膜新生血管形成。RNA 测序数据表明,骨粘连蛋白参与了这一过程。GQDs 通过 STAT3 抑制骨粘连蛋白的表达,并通过 ERK 途径进一步调节细胞周期相关蛋白水平。该信号通路在 OIR 小鼠模型中得到了证实。
本研究表明,GQDs 可通过破坏骨粘连蛋白/ERK 途径和随后的细胞周期,成为一种治疗病理性视网膜新生血管形成的生物相容性抗血管生成纳米药物。