MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization
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 r...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/2/243 |
| _version_ | 1797477292547506176 |
|---|---|
| author | Jouri S. Alanazi Fulwah Yahya Alqahtani Fadilah Sfouq Aleanizy Awwad A. Radwan Ahmed Bari Qamraa Hamad Alqahtani Hosam Gharib Abdelhady Ibrahim Alsarra |
| author_facet | Jouri S. Alanazi Fulwah Yahya Alqahtani Fadilah Sfouq Aleanizy Awwad A. Radwan Ahmed Bari Qamraa Hamad Alqahtani Hosam Gharib Abdelhady Ibrahim Alsarra |
| author_sort | Jouri S. Alanazi |
| collection | DOAJ |
| description | 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 <sup>1</sup>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. |
| first_indexed | 2024-03-09T21:15:31Z |
| format | Article |
| id | doaj.art-ffb3d6f5d9244b08879f6c998fc430c9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:15:31Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ffb3d6f5d9244b08879f6c998fc430c92023-11-23T21:36:03ZengMDPI AGPharmaceutics1999-49232022-01-0114224310.3390/pharmaceutics14020243MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal NeovascularizationJouri S. Alanazi0Fulwah Yahya Alqahtani1Fadilah Sfouq Aleanizy2Awwad A. Radwan3Ahmed Bari4Qamraa Hamad Alqahtani5Hosam Gharib Abdelhady6Ibrahim Alsarra7Pharmaceutical Care Department, National Guard Health Affairs, Riyadh 11426, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaKayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaCollege of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USADepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaChoroidal 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 <sup>1</sup>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.https://www.mdpi.com/1999-4923/14/2/243choroidal neovascularizationinternalizing RGD peptidepolylactic-co-glycolic acid nanoparticlesmiR-539angiogenesis |
| spellingShingle | Jouri S. Alanazi Fulwah Yahya Alqahtani Fadilah Sfouq Aleanizy Awwad A. Radwan Ahmed Bari Qamraa Hamad Alqahtani Hosam Gharib Abdelhady Ibrahim Alsarra MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization Pharmaceutics choroidal neovascularization internalizing RGD peptide polylactic-co-glycolic acid nanoparticles miR-539 angiogenesis |
| title | MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization |
| title_full | MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization |
| title_fullStr | MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization |
| title_full_unstemmed | MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization |
| title_short | MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization |
| title_sort | microrna 539 5p loaded plga nanoparticles grafted with irgd as a targeting treatment for choroidal neovascularization |
| topic | choroidal neovascularization internalizing RGD peptide polylactic-co-glycolic acid nanoparticles miR-539 angiogenesis |
| url | https://www.mdpi.com/1999-4923/14/2/243 |
| work_keys_str_mv | AT jourisalanazi microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT fulwahyahyaalqahtani microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT fadilahsfouqaleanizy microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT awwadaradwan microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT ahmedbari microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT qamraahamadalqahtani microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT hosamgharibabdelhady microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization AT ibrahimalsarra microrna5395ploadedplgananoparticlesgraftedwithirgdasatargetingtreatmentforchoroidalneovascularization |