Nanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul 34956, Turkey.
Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul 34956, Turkey.
ACS Appl Bio Mater. 2024 Sep 16;7(9):6001-6013. doi: 10.1021/acsabm.4c00585. Epub 2024 Aug 21.
Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.
年龄相关性黄斑变性（AMD）是一种眼部疾病，可导致老年患者视力受损，目前的治疗方法包括反复注射单克隆抗体血管内皮生长因子（anti-VEGF）抑制剂。本研究探讨了一种肽类抗 VEGF 分子的纳米制剂治疗新生血管性 AMD 的潜力。具有高 VEGF-Fc 受体亲和力的抗 VEGF 肽 HRHTKQRHTALH（HRH）被用作生物活性药物来控制视网膜新生血管。通过将二乙烯砜和胆固醇掺入其中来增加纳米药物的稳定性和控制其尺寸，生成了由透明质酸纳米凝胶组成的纳米制剂。纳米凝胶的包封效率为 65%，在 192 h 结束时药物释放了 34.72%。所得纳米凝胶在 15 min 内被人脐静脉内皮细胞（HUVEC）和 ARPE-19 细胞有效内化，结果表明纳米制剂对 ARPE-19 细胞没有毒性，而由于纳米凝胶结构中的抗 VEGF 肽，它抑制了 HUVEC 的增殖。在模拟视网膜穿透的共培养实验中，观察到纳米凝胶到达 HUVEC 并对其增殖产生负面影响，而不会干扰 ARPE-19 细胞的单层。鸡胚绒毛尿囊膜实验表明，与游离 HRH 相比，纳米凝胶制剂具有更高的抗血管生成活性。此外，在氧诱导的视网膜病变模型中，用载有 HRH 的纳米凝胶处理的小鼠的血管过度生长明显受到抑制。这项研究表明，本研究中制备的纳米凝胶是治疗 AMD 的局部治疗的有前途的候选药物。
