PDF(Pubmed)
Abstract：
Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
摘要：
角膜新生血管(CNV)是世界范围内常见的致盲因素之一。导致视力下降甚至失明。然而,目前的治疗方法如手术干预和抗VEGF药物治疗仍存在一些不足或引起一些不良反应。最近,SU6668，一种靶向血管生成酪氨酸激酶的抑制剂，已经证明了对新血管形成的生长抑制。但其疏水性和低的眼部生物利用度限制了其在角膜中的应用。特此,我们建议使用超稳定的纯纳米药物配方技术（SPFT）制备SU6668纯纳米颗粒（NanoSU6668；尺寸〜135nm），在1mg/mL时具有均匀的粒径和优异的水分散体。此外，将间充质干细胞膜囊泡(MSCm)包被在NanoSU6668表面,然后与TAT细胞穿透肽偶联,制备多功能TAT-MSCm@NanoSU6668(T-MNS)。通过滴眼液处理浓度为200µg/mL的T-MNS的CNV，并以高靶向性能积聚在血管中，治疗4天后可消除血管并恢复角膜透明度。同时,药物安全性测试证实，T-MNS没有对角膜造成任何损害，视网膜和其他眼组织。总之,T-MNS滴眼液具有在低给药频率下有效和安全地治疗CNV的潜力，为CNV疗法开辟了新天地。
