APRPG-modified nanoliposome loaded with miR-146a-5p inhibitor suppressed choroidal neovascularization by targeting endothelial cells

Abstract

Introduction To explore the effect and mechanism of APRPG-modified nanoliposomes loaded with miR-146a-5p inhibitor (ANL-miR-146a-5p inhibitor) on endothelial cell proliferation, migration, tube formation, and choroidal neovascularization (CNV) in mice. Methods ANL-miR-146a-5p inhibitors were generated by thin film hydration; in vitro, endothelial cell uptake experiment was used to detect the targeting effect of ANL-miR-146a-5p inhibitor; endothelial cells proliferation, migration, and tube formation were detected, respectively, by CCK8 assay, scratch assay, and Matrigel tube formation assay. In vivo, the mice CNV models were established by 810 nm laser photocoagulation. Mice choroidal flatmounts were performed to detect the volume of CNV after intravitreal injection of L-miR-146a-5p inhibitor, ANL-miR-146a-5p inhibitor, or normal saline; the vascular endothelial growth factor (VEGF) expression of mice choroidal tissue was detected by ELISA; HE section and electrophysiology (ERG) were performed to check the toxicity of ANL-miR-146a-5p inhibitor on mice retina. Results ANL are targeted to endothelial cells and are more targeted in inflammatory environment. At the same concentration, ANL-miR-146a-5p inhibitor’s ability to inhibit endothelial cell proliferation, migration, tube formation, CNV formation, and VEGF expression is better than L-miR-146a-5p inhibitor (p < 0.05); ANL-miR-146a-5p inhibitor had no toxicity on the structure of mouse retina; ANL-miR-146a-5p inhibitor had no toxicity on the a-wave and b-wave amplitudes and b-wave implicit times (p > 0.05). Conclusions ANL-miR-146a-5p inhibitor can more effectively down-regulate the expression level of VEGF through its targeting to endothelial cells, thereby more effectively inhibiting endothelial cell proliferation, migration, tube formation, and mice CNV formation.