Abstract
Purpose :
To fabricate membrane cloaked biomimetic nanoparticles ([RBC-EC] NPs) using red blood cell and endothelial cell membranes, and to verify their protective effect on diabetic retinal vascular injury for the targeted and noninvasive treatment of early diabetic retinopathy.
Methods :
[RBC-EC] NPs were prepared and characterized by various techniques. In vitro targeting, anti-phagocytosis, anti-endothelial cell migration, and cytotoxicity assays were performed. A streptozotocin-induced diabetic rat model was established and treated with [RBC-EC] NPs or PBS via intravenous injection at 3 months of hyperglycemia. Retinal vascular morphology, permeability, capillary injury, and vascular endothelial growth factor expression were evaluated. Blood routine, blood biochemistry, and histopathology of major organs were also examined.
Results :
[RBC-EC] NPs showed a core-shell structure with a diameter of 80.1 ± 12.4 nm and a membrane thickness of 5.9 ± 1.3 nm. In vitro, they exhibited 10 times higher targeting and anti-migrating abilities to retinal microvascular endothelial cells compares to RBC membrane clocked NPs, and 9 times higher of anti-phagocytosis abilities to RAW264.7 compares to EC membrane clocked NPs. In vivo, [RBC-EC] NPs was retained in rat retinal blood vessels for 1 day after intravenous injection, they effectively improve the abnormal shape, leakage, and damage of blood vessels in diabetic rats after 6 times treatment for 10 days. They also reduced the expression of vascular endothelial growth factor A in the retina, and improved the liver and kidney function of diabetic rats with no obvious toxic or side effects.
Conclusions :
[RBC-EC] NPs are safe and have the potential to treat early diabetic retinopathy by protecting the retinal vascular injury.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.