{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:07:41Z","timestamp":1789564061846,"version":"build-2803163510"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.<\/jats:p>","DOI":"10.3390\/biom15111592","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges"],"prefix":"10.3390","volume":"15","author":[{"given":"Michele","family":"Nardella","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Ophthalmology, Ospedali Privati Forl\u00ec \u201cVilla Igea\u201d, 47122 Forl\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-6941","authenticated-orcid":false,"given":"Marco","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Ophthalmology, Ospedali Privati Forl\u00ec \u201cVilla Igea\u201d, 47122 Forl\u00ec, Italy"},{"name":"Ophthalmology Clinic Operating Unit, Head and Neck Department, Sant\u2019Anna University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5654-3942","authenticated-orcid":false,"given":"Angeli Christy","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Ophthalmology, Ospedali Privati Forl\u00ec \u201cVilla Igea\u201d, 47122 Forl\u00ec, Italy"},{"name":"Istituto Internazionale per la Ricerca e Formazione in Oftalmologia (IRFO), 47122 Forl\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginevra Giovanna","family":"Adamo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Ophthalmology Clinic Operating Unit, Head and Neck Department, Sant\u2019Anna University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mura","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Ophthalmology Clinic Operating Unit, Head and Neck Department, Sant\u2019Anna University Hospital, 44124 Ferrara, Italy"},{"name":"Department of Vitreoretinal and Uveitis Divisions, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-3521","authenticated-orcid":false,"given":"Massimo","family":"Busin","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Ophthalmology, Ospedali Privati Forl\u00ec \u201cVilla Igea\u201d, 47122 Forl\u00ec, Italy"},{"name":"Istituto Internazionale per la Ricerca e Formazione in Oftalmologia (IRFO), 47122 Forl\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.fmre.2023.08.011","article-title":"The retinal pigment epithelium: Functions and roles in ocular diseases","volume":"4","author":"Wang","year":"2024","journal-title":"Fundam. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"802","DOI":"10.2174\/156652410793937813","article-title":"The Retinal Pigment Epithelium in Health and Disease","volume":"10","author":"Sparrrow","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for Neovascular Age-Related Macular Degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65 -mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.4103\/ijo.IJO_3117_20","article-title":"Gene therapy in retinal diseases: A review","volume":"69","author":"Dhurandhar","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mostafa, M., Al Fatease, A., Alany, R.G., and Abdelkader, H. (2023). Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061746"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Varela-Fern\u00e1ndez, R., D\u00edaz-Tom\u00e9, V., Luaces-Rodr\u00edguez, A., Conde-Penedo, A., Garc\u00eda-Otero, X., Luzardo-\u00c1lvarez, A., Fern\u00e1ndez-Ferreiro, A., and Otero-Espinar, F.J. (2020). Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030269"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116902","DOI":"10.1016\/j.bcp.2025.116902","article-title":"Advancements in age-related macular degeneration treatment: From traditional anti-VEGF to emerging therapies in gene, stem cell, and nanotechnology","volume":"236","author":"Wang","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1021\/acsnano.2c05824","article-title":"Highly Retina-Permeating and Long-Acting Resveratrol\/Metformin Nanotherapeutics for Enhanced Treatment of Macular Degeneration","volume":"17","author":"Nguyen","year":"2023","journal-title":"ACS Nano"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2401613","DOI":"10.1002\/adhm.202401613","article-title":"Melanin-Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age-Related Macular Degeneration","volume":"13","author":"Huang","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eadj0006","DOI":"10.1126\/sciadv.adj0006","article-title":"Dynamically covalent lipid nanoparticles mediate CRISPR-Cas9 genome editing against choroidal neovascularization in mice","volume":"11","author":"Cao","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gabai, A., Zeppieri, M., Finocchio, L., and Salati, C. (2023). Innovative Strategies for Drug Delivery to the Ocular Posterior Segment. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071862"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gade, S., So, Y., Mishra, D., Baviskar, S.M., Assiri, A.A., Glover, K., Sheshala, R., Vora, L.K., and Thakur, R.R.S. (2025). Ocular Drug Delivery: Emerging Approaches and Advances. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17050599"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/17425247.2021.1867532","article-title":"Biomechanics of suprachoroidal drug delivery: From benchtop to clinical investigation in ocular therapies","volume":"18","author":"Hancock","year":"2021","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wu, K.Y., Fujioka, J.K., Gholamian, T., Zaharia, M., and Tran, S.D. (2023). Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery. Pharmaceuticals, 16.","DOI":"10.3390\/ph16091241"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, K.Y., Gao, A., Giunta, M., and Tran, S.D. (2024). What\u2019s New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023. Pharmaceuticals, 17.","DOI":"10.3390\/ph17081007"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.drudis.2019.05.005","article-title":"Intravitreal nanoparticles for retinal delivery","volume":"24","author":"Huang","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1016\/j.drudis.2022.05.024","article-title":"Targeted drug delivery to the retinal pigment epithelium: Untapped therapeutic potential for retinal diseases","volume":"27","author":"Bohley","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"126009","DOI":"10.1016\/j.ijpharm.2025.126009","article-title":"Revolutionizing age-related macular degeneration treatment: Advances and future directions in non-invasive retinal drug delivery systems","volume":"683","author":"Sahu","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ophtha.2023.12.033","article-title":"Risk of Endophthalmitis Based on Cumulative Number of Anti-VEGF Intravitreal Injections","volume":"131","author":"Israilevich","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/ICU.0000000000000850","article-title":"Complications of intravitreal injections: 2022","volume":"33","author":"Patel","year":"2022","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7158","DOI":"10.1016\/j.biomaterials.2013.06.002","article-title":"A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium","volume":"34","author":"Koirala","year":"2013","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Irigoyen, C., Alonso, A.A., Sanchez-Molina, J., Rodr\u00edguez-Hidalgo, M., Lara-L\u00f3pez, A., and Ruiz-Ederra, J. (2022). Subretinal Injection Techniques for Retinal Disease: A Review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11164717"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.oret.2024.11.019","article-title":"Characteristics and Risks of Endophthalmitis after 25-gauge Vitrectomy Surgery over a 14-year Period","volume":"9","author":"Miller","year":"2024","journal-title":"Ophthalmol. Retin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/ICU.0000000000000660","article-title":"Gene therapy beyond luxturna: A new horizon of the treatment for inherited retinal disease","volume":"31","author":"Prado","year":"2020","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejpb.2019.08.008","article-title":"Role of retinal pigment epithelium permeability in drug transfer between posterior eye segment and systemic blood circulation","volume":"143","author":"Ramsay","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/978-1-4614-4711-5_3","article-title":"The blood-retina barrier: Tight junctions and barrier modulation","volume":"763","author":"Campbell","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","first-page":"1","article-title":"Nanotechnology-based ocular drug delivery systems: Recent advances and future prospects","volume":"21","author":"Li","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2174\/1389450043345407","article-title":"Drug Delivery Systems: Past, Present, and Future","volume":"5","author":"Mainardes","year":"2004","journal-title":"Curr. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rehan, F., Zhang, M., Fang, J., and Greish, K. (2024). Therapeutic Applications of Nanomedicine: Recent Developments and Future Perspectives. Molecules, 29.","DOI":"10.3390\/molecules29092073"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1219054","DOI":"10.3389\/fbioe.2023.1219054","article-title":"The application of nanomedicine in clinical settings","volume":"11","author":"Zhao","year":"2023","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3390\/jfb6020277","article-title":"Nanomedicine Approaches for Corneal Diseases","volume":"6","author":"Chaurasia","year":"2015","journal-title":"J. Funct. Biomater."},{"key":"ref_33","first-page":"1038","article-title":"Nanotechnology in retinal drug delivery","volume":"11","author":"Jiang","year":"2018","journal-title":"Int. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1080\/1061186X.2021.1878366","article-title":"A review of nanocarrier-mediated drug delivery systems for posterior segment eye disease: Challenges analysis and recent advances","volume":"29","author":"Wang","year":"2021","journal-title":"J. Drug Target."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2304626","DOI":"10.1002\/adhm.202304626","article-title":"Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management","volume":"13","author":"Zhou","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mahaling, B., Low, S.W.Y., Ch, S., Addi, U.R., Ahmad, B., Connor, T.B., Mohan, R.R., Biswas, S., and Chaurasia, S.S. (2023). Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15072005"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Nikolaidou, A., Spyratou, E., Sandali, A., Gianni, T., Platoni, K., Lamprogiannis, L., and Efstathopoulos, E.P. (2025). Utilization of Nanoparticles for Treating Age-Related Macular Degeneration. Pharmaceuticals, 18.","DOI":"10.3390\/ph18020162"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41565-020-0696-3","article-title":"Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy","volume":"15","author":"Manfredi","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27835","DOI":"10.1039\/D0RA04971A","article-title":"Nanocarriers for ocular drug delivery: Current status and translational opportunity","volume":"10","author":"Gorantla","year":"2020","journal-title":"RSC Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jconrel.2010.08.028","article-title":"Barrier analysis of periocular drug delivery to the posterior segment","volume":"148","author":"Ranta","year":"2010","journal-title":"J. Control Release"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1147037","DOI":"10.3389\/fimmu.2023.1147037","article-title":"The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders","volume":"14","author":"Biasella","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41427-023-00478-9","article-title":"Development of nanodrug-based eye drops with good penetration properties and ROS responsiveness for controllable release to treat fungal keratitis","volume":"15","author":"Niu","year":"2023","journal-title":"NPG Asia Mater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"513","DOI":"10.4103\/1673-5374.350192","article-title":"Inflammation and retinal degenerative diseases","volume":"18","author":"Kaur","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Caban, M., Owczarek, K., and Lewandowska, U. (2022). The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084256"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2207335","DOI":"10.1002\/smll.202207335","article-title":"MMP9-Responsive Graphene Oxide Quantum Dot-Based Nano-in-Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization","volume":"19","author":"Huang","year":"2023","journal-title":"Small"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41565-022-01085-5","article-title":"A transistor-like pH-sensitive nanodetergent for selective cancer therapy","volume":"17","author":"Liu","year":"2022","journal-title":"Nat. Nanotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.2147\/IJN.S195504","article-title":"Mesoporous silica nanoparticles as a delivery system for improving antiangiogenic therapy","volume":"14","author":"Sun","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Deng, S., Gigliobianco, M.R., Censi, R., and Di Martino, P. (2020). Polymeric Nanocapsules as Nanotechnological Alternative for Drug Delivery System: Current Status, Challenges and Opportunities. Nanomaterials, 10.","DOI":"10.3390\/nano10050847"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"020902","DOI":"10.1063\/5.0264382","article-title":"Recent advancements in polymer science for retinal diseases: New frontiers in drug delivery systems","volume":"9","author":"Wang","year":"2025","journal-title":"APL Bioeng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1002\/jbm.a.35446","article-title":"Albuminated Plga Nanoparticles for Ocular Neovascularization Treatment","volume":"103","author":"Varshochian","year":"2015","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/jop.2012.0128","article-title":"Lipid Nanoparticles as Drug\/Gene Delivery Systems to the Retina","volume":"29","author":"Delgado","year":"2013","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4103\/1735-5362.235156","article-title":"Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages","volume":"13","author":"Ghasemiyeh","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117108","DOI":"10.1016\/j.biopha.2024.117108","article-title":"Advances in the development of lipid nanoparticles for ophthalmic therapeutics","volume":"178","author":"Chen","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-023-42189-3","article-title":"Lipid nanoparticles with PEG-variant surface modifications mediate genome editing in the mouse retina","volume":"14","author":"Gautam","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1016\/j.celrep.2018.02.014","article-title":"A Single Administration of CRISPR\/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing","volume":"22","author":"Finn","year":"2018","journal-title":"Cell Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.addr.2020.06.002","article-title":"Lipid nanoparticles for nucleic acid delivery: Current perspectives","volume":"154\u2013155","author":"Samaridou","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.3390\/ijms15011590","article-title":"Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE)","volume":"15","author":"Giannaccini","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1021\/acsabm.3c01289","article-title":"Smart Nanocarriers for the Treatment of Retinal Diseases","volume":"7","author":"Liu","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yang, B., Li, G., Liu, J., Li, X., Zhang, S., Sun, F., and Liu, W. (2021). Nanotechnology for Age-Related Macular Degeneration. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122035"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Huang, L., Liang, W., Zhou, K., Wassel, R.A., Ridge, Z.D., Ma, J.-X., and Wang, B. (2021). Therapeutic Effects of Fenofibrate Nano-Emulsion Eye Drops on Retinal Vascular Leakage and Neovascularization. Biology, 10.","DOI":"10.3390\/biology10121328"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jconrel.2011.11.022","article-title":"Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: An in-vivo study in rats and mice","volume":"160","author":"Hagigit","year":"2012","journal-title":"J. Control Release"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"652","DOI":"10.4274\/tjps.galenos.2020.59319","article-title":"Nanoemulsions as Ophthalmic Drug Delivery Systems","volume":"18","author":"Dhahir","year":"2021","journal-title":"Turk. J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2017.01.012","article-title":"Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies","volume":"248","author":"Mandal","year":"2017","journal-title":"J. Control Release"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Osipova, O., Sharoyko, V., Zashikhina, N., Zakharova, N., Tennikova, T., Urtti, A., and Korzhikova-Vlakh, E. (2020). Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010039"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"732340","DOI":"10.1155\/2013\/732340","article-title":"Dendrimeric Systems and Their Applications in Ocular Drug Delivery","volume":"2013","author":"Yavuz","year":"2013","journal-title":"Sci. World J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41433-020-0770-y","article-title":"Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases","volume":"34","author":"Seah","year":"2020","journal-title":"Eye"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.2147\/IJN.S24447","article-title":"Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells","volume":"6","author":"Chen","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/jphp.12940","article-title":"Hyaluronic acid-modified cationic niosomes for ocular gene delivery: Improving transfection efficiency in retinal pigment epithelium","volume":"70","author":"Qin","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"505101","DOI":"10.1088\/0957-4484\/20\/50\/505101","article-title":"Intravenously administered gold nanoparticles pass through the blood\u2013retinal barrier depending on the particle size, and induce no retinal toxicity","volume":"20","author":"Kim","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Laradji, A., Karakocak, B.B., Kolesnikov, A.V., Kefalov, V.J., and Ravi, N. (2021). Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium. Polymers, 13.","DOI":"10.3390\/polym13193324"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Galindo-Camacho, R.M., Blanco-Llamero, C., da Ana, R., Fuertes, M.A., Se\u00f1or\u00e1ns, F.J., Silva, A.M., Garc\u00eda, M.L., and Souto, E.B. (2022). Therapeutic Approaches for Age-Related Macular Degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911769"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.2147\/IJN.S157000","article-title":"DNA nanoparticles are safe and nontoxic in non-human primate eyes","volume":"13","author":"Conley","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1477-3155-12-5","article-title":"Engineered nanoparticles interacting with cells: Size matters","volume":"12","author":"Shang","year":"2014","journal-title":"J. Nanobiotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"931759","DOI":"10.3389\/fmolb.2022.931759","article-title":"Nanoparticles in ocular applications and their potential toxicity","volume":"9","author":"Yang","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1016\/j.biomaterials.2012.01.030","article-title":"The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection","volume":"33","author":"Koo","year":"2012","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1021\/acs.molpharmaceut.6b00864","article-title":"Effective Retinal Penetration of Lipophilic and Lipid-Conjugated Hydrophilic Agents Delivered by Engineered Liposomes","volume":"14","author":"Lee","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1167\/iovs.14-16250","article-title":"Systemic and Intravitreal Delivery of Dendrimers to Activated Microglia\/Macrophage in Ischemia\/Reperfusion Mouse Retina","volume":"56","author":"Kambhampati","year":"2015","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/nnano.2012.207","article-title":"Biomolecular coronas provide the biological identity of nanosized materials","volume":"7","author":"Monopoli","year":"2012","journal-title":"Nat. Nanotechnol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5978","DOI":"10.1016\/j.biomaterials.2013.04.035","article-title":"Hyaluronan-modified core\u2013shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection","volume":"34","author":"Gan","year":"2013","journal-title":"Biomaterials"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jconrel.2017.02.013","article-title":"Differentially cleaving peptides as a strategy for controlled drug release in human retinal pigment epithelial cells","volume":"251","author":"Bhattacharya","year":"2017","journal-title":"J. Control Release"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jconrel.2017.09.036","article-title":"High-density lipoprotein mutant eye drops for the treatment of posterior eye diseases","volume":"266","author":"Suda","year":"2017","journal-title":"J. Control Release"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/gt.2008.185","article-title":"Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV","volume":"16","author":"Singh","year":"2009","journal-title":"Gene Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jconrel.2024.07.022","article-title":"ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases","volume":"373","author":"Elbedwehy","year":"2024","journal-title":"J. Control Release"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"srep43092","DOI":"10.1038\/srep43092","article-title":"Magnetic nanoparticles: A strategy to target the choroidal layer in the posterior segment of the eye","volume":"7","author":"Giannaccini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1021\/acsabm.0c00130","article-title":"Stable Retinoid Analogue Targeted Dual pH-Sensitive Smart Lipid ECO\/pDNA Nanoparticles for Specific Gene Delivery in the Retinal Pigment Epithelium","volume":"3","author":"Sun","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ijpharm.2018.05.056","article-title":"Smart liposomal drug delivery for treatment of oxidative stress model in human embryonic stem cell-derived retinal pigment epithelial cells","volume":"548","author":"Behroozi","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.biomaterials.2011.10.010","article-title":"Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration","volume":"33","author":"Iezzi","year":"2012","journal-title":"Biomaterials"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sapowadia, A., Ghanbariamin, D., Zhou, L., Zhou, Q., Schmidt, T., Tamayol, A., and Chen, Y. (2023). Biomaterial Drug Delivery Systems for Prominent Ocular Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071959"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/17425247.2020.1735348","article-title":"Penetratin-modified lutein nanoemulsion in-situ gel for the treatment of age-related macular degeneration","volume":"17","author":"Ge","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jddst.2016.10.009","article-title":"Preparation and characterization of a lutein loading nanoemulsion system for ophthalmic eye drops","volume":"36","author":"Lim","year":"2016","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1159\/000524942","article-title":"Pathophysiology of Age-Related Macular Degeneration: Implications for Treatment","volume":"65","author":"Sanabria","year":"2022","journal-title":"Ophthalmic Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jconrel.2024.06.047","article-title":"Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis","volume":"372","author":"Cao","year":"2024","journal-title":"J. Control Release"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1001\/jamaophthalmol.2022.1640","article-title":"Long-term Outcomes of Adding Lutein\/Zeaxanthin and \u03c9-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression","volume":"140","author":"Chew","year":"2022","journal-title":"JAMA Ophthalmol"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2300062","DOI":"10.1002\/anbr.202300062","article-title":"Mesoporous Cerium Oxide Nanoparticles with High Scavenging Properties of Reactive Oxygen Species for Treating Age-Related Macular Degeneration","volume":"3","author":"Choi","year":"2023","journal-title":"Adv. NanoBiomed Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/jop.2010.0158","article-title":"Comparison of Long-Acting Bevacizumab Formulations in the Treatment of Choroidal Neovascularization in a Rat Model","volume":"27","author":"Pan","year":"2011","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/1874364101206010054","article-title":"Controlled Release of Bevacizumab Through Nanospheres for Extended Treatment of Age-Related Macular Degeneration","volume":"6","author":"Li","year":"2012","journal-title":"Open Ophthalmol. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1517\/17425247.4.4.371","article-title":"Novel approaches to retinal drug delivery","volume":"4","author":"Janoria","year":"2007","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e44804","DOI":"10.1097\/MD.0000000000044804","article-title":"Pathogenic mechanisms and treatment advances in proliferative vitreoretinopathy: A review","volume":"104","author":"Dai","year":"2025","journal-title":"Medicine"},{"key":"ref_100","first-page":"124","article-title":"Nanoparticles for gene delivery to retinal pigment epithelial cells","volume":"11","author":"Bejjani","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2147\/nano.2007.2.1.65","article-title":"Age-related macular degeneration: A target for nanotechnology derived medicines","volume":"2","author":"Birch","year":"2007","journal-title":"Int. J. Nanomed."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1167\/iovs.10-5891","article-title":"A Lipid Nanoparticle System Improves siRNA Efficacy in RPE Cells and a Laser-Induced Murine CNV Model","volume":"52","author":"Liu","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_103","first-page":"2613","article-title":"Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery","volume":"8","author":"Chen","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/tvst.13.7.7","article-title":"Lipid Nanoparticle-Mediated Delivery of mRNA into the Mouse and Human Retina and Other Ocular Tissues","volume":"13","author":"Chambers","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"eadd4623","DOI":"10.1126\/sciadv.add4623","article-title":"Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates","volume":"9","author":"Ryals","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e7410","DOI":"10.1371\/journal.pone.0007410","article-title":"Ocular Delivery of Compacted DNA-Nanoparticles Does Not Elicit Toxicity in the Mouse Retina","volume":"4","author":"Ding","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e5290","DOI":"10.1371\/journal.pone.0005290","article-title":"A Partial Structural and Functional Rescue of a Retinitis Pigmentosa Model with Compacted DNA Nanoparticles","volume":"4","author":"Cai","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijpharm.2008.04.023","article-title":"Solid lipid nanoparticles for retinal gene therapy: Transfection and intracellular trafficking in RPE cells","volume":"360","author":"Delgado","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"120499","DOI":"10.1016\/j.ijpharm.2021.120499","article-title":"Emerging innovations in nano-enabled therapy against age-related macular degeneration: A paradigm shift","volume":"600","author":"Dubey","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.bbrc.2015.08.023","article-title":"Regulatory aspects on nanomedicines","volume":"468","author":"Sainz","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1167\/iovs.13-13707","article-title":"Drug and Gene Delivery to the Back of the Eye: From Bench to Bedside","volume":"55","author":"Durazo","year":"2014","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.apsb.2016.09.001","article-title":"Nanotechnology-based strategies for treatment of ocular disease","volume":"7","author":"Weng","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3389\/fchem.2018.00360","article-title":"Nanomedicine: Principles, Properties, and Regulatory Issues","volume":"6","author":"Soares","year":"2018","journal-title":"Front. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:44:49Z","timestamp":1763027089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":113,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111592"],"URL":"https:\/\/doi.org\/10.3390\/biom15111592","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]}}}