Alanazi Jouri S, Alqahtani Fulwah Yahya, Aleanizy Fadilah Sfouq, Radwan Awwad A, Bari Ahmed, Alqahtani Qamraa Hamad, Abdelhady Hosam Gharib, Alsarra Ibrahim
Pharmaceutical Care Department, National Guard Health Affairs, Riyadh 11426, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Pharmaceutics. 2022 Jan 20;14(2):243. doi: 10.3390/pharmaceutics14020243.
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 H 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.
脉络膜新生血管（CNV）是导致视力损害的主要原因，它是由眼部脉络膜血管过度生长引起的。目前针对这种病症的治疗方法临床疗效有限，因此需要出现新的治疗方式，如微小RNA（miRNA）。最近一项研究在CNV动物模型中确定微小RNA - 539 - 5p（miR - 539）为血管生成抑制剂；然而，其治疗递送存在局限性。因此，本研究旨在将miR - 539配制于由聚乳酸 - 乙醇酸共聚物（PLGA）制备的靶向纳米颗粒（NP）中。这些纳米颗粒用可内化的精氨酰甘氨酰天冬氨酸（RGD）肽（iRGD）修饰，该肽特异性靶向α - v - β - 3（αvβ3）整合素受体，这种受体在CNV患者眼部组织血管中过表达。1H NMR光谱结果显示iRGD肽成功偶联到PLGA纳米颗粒中。制备了miR - 539 - PLGA.NP和miR - 539 - iRGD - PLGA.NP，其粒径分别为300±3和306.40±4nm。用掺入PLGA纳米颗粒和iRGD - PLGA.NP中的miR - 539转染后48小时和72小时，人视网膜微血管内皮细胞（HRMEC）活力降低。与普通纳米颗粒相比，iRGD功能化的PLGA纳米颗粒导致细胞活力进一步显著降低，表明iRGD接枝纳米颗粒对纳米颗粒摄取有增强作用。当前研究表明，miR - 539 - PLGA.NP和miR - 539 - iRGD - PLGA.NP是有前景的方法，可降低HRMEC的活力，提示它们在治疗CNV方面的治疗潜力。
