MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization.

Ahmed Bari,Qamraa Hamad Alqahtani,Jouri S Alanazi,Ibrahim Alsarra,Fulwah Yahya Alqahtani,Fadilah Sfouq Aleanizy,Hosam Gharib Abdelhady,Awwad A Radwan

doi:10.3390/pharmaceutics14020243

Abstract

Choroidal neovascularization (CNV) is a major cause of visual impairment that results from excessive growth of blood vessels in the eye’s choroid. The limited clinical efficacy of the current therapy for this condition requires the emergence of new treatment modalities such as microRNA (miRNAs). A recent study identified microRNA-539-5p (miR-539) as an angiogenic suppressor in a CNV animal model; however, its therapeutic delivery is limited. Therefore, this study aims to formulate miR-539 in targeted nanoparticles (NPs) prepared from polylactic-co-glycolic acid (PLGA). The NPs were decorated with internalizing arginylglycylaspartic (RGD) peptide (iRGD), which specifically targets the alpha-v-beta-3 (αvβ3) integrin receptor that is overexpressed in blood vessels of ocular tissue in CNV patients. The 1H NMR spectra results revealed successful conjugation of iRGD peptide into PLGA NPs. The miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs were prepared and showed a particle size of 300 ± 3 and 306.40 ± 4 nm, respectively. A reduction in human retinal microvascular endothelial cell (HRMEC) viability was shown 48 and 72 h post transfection with miR-539 incorporated in PLGA NPs and iRGD-PLGA.NPs. iRGD-functionalized PLGA NPs caused further significant reduction in cell viability when compared with plain ones, revealing an enhancement in the NP uptake with iRGD-grafted NPs. The current study showed that miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs are promising approaches that reduced the viability of HRMECs, suggesting their therapeutic potential in the treatment of CNV.

Highlights

Licensee MDPI, Basel, Switzerland.Choroidal neovascularization (CNV) is defined as growth of new blood vessels that originates from the choroid and extends into the subretinal pigment epithelium or subretinal space or both
Conjugation of internalizing arginylglycylaspartic (RGD) peptide (iRGD) peptide to the surface of polylactic-co-glycolic acid (PLGA) polymer was carried out as described previously [17] via a two-step process in which the polymer first was activated by sulfo N-hydroxy succinimide (NHS)/EDAC, NH2 of iRGD was attached to the activated polymer, forming a functionalized PLGA polymer
1 H nuclear magnetic resonance (NMR) spectroscopy was used to characterize the conjugation between iRGD and PLGA

Summary

Introduction

Choroidal neovascularization (CNV) is defined as growth of new blood vessels that originates from the choroid and extends into the subretinal pigment epithelium or subretinal space or both. CNV is a major cause of visual impairment due to leakage of immature blood vessels and subsequent fibrosis [1,2]. Current treatment of CNV involves vascular endothelial growth factor (VEGF) antagonists, such as bevacizumab and ranibizumab. Resistance to such monotherapy resulted in loss in visual acuity in a subset of published maps and institutional affil-.

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