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.

Keywords:

• Choroidal neovascularization
• APRPG
• nanoliposomes
• miR-146a-5p
• VEGF

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from National Natural Science Foundation of China (81670866, 81600741), Basic Research Plan of Guangzhou Science and Technology Plan Project (202002030380), Fundamental Research Funds for the Central Universities (Sun Yat-sen University, 19ykpy152), the Natural Science Foundation of Guangdong Province (2020A1515011099), and the Science and Technology Planning Project of Guangdong Province (2017A020215038).