{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:48:50Z","timestamp":1772761730724,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCT","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"FCT\/MCT","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"FCT\/MCT","award":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"]}]},{"name":"Bolsa de Inova\u00e7\u00e3o da SR Sul e Regi\u00f5es Aut\u00f3nomas da Ordem dos Farmac\u00eauticos (BInov 2021)","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Bolsa de Inova\u00e7\u00e3o da SR Sul e Regi\u00f5es Aut\u00f3nomas da Ordem dos Farmac\u00eauticos (BInov 2021)","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"Bolsa de Inova\u00e7\u00e3o da SR Sul e Regi\u00f5es Aut\u00f3nomas da Ordem dos Farmac\u00eauticos (BInov 2021)","award":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"]}]},{"name":"Santander Totta\u2014Bolsas de Incentivo a Doutoramento (BID)\u2014UBI-Santander Totta 2022, Faculdade de Ci\u00eancias","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Santander Totta\u2014Bolsas de Incentivo a Doutoramento (BID)\u2014UBI-Santander Totta 2022, Faculdade de Ci\u00eancias","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"Santander Totta\u2014Bolsas de Incentivo a Doutoramento (BID)\u2014UBI-Santander Totta 2022, Faculdade de Ci\u00eancias","award":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer\u2013ligand complexes are highly stable, presenting melting temperatures from 45 \u00b0C to 60 \u00b0C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments.<\/jats:p>","DOI":"10.3390\/ph16050751","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-3310","authenticated-orcid":false,"given":"David","family":"Moreira","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"J\u00e9ssica","family":"Lopes-Nunes","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-1504","authenticated-orcid":false,"given":"F\u00e1tima Milhano","family":"Santos","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Calle Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain"}]},{"given":"Maria Paula Cabral","family":"Campello","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5708-3885","authenticated-orcid":false,"given":"Maria Cristina","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-0913","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Paulo","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0927-2331","authenticated-orcid":false,"given":"C\u00e2ndida","family":"Tomaz","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departamento de Qu\u00edmica, Universityof Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-1242","authenticated-orcid":false,"given":"Carla","family":"Cruz","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departamento de Qu\u00edmica, Universityof Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev-vision-082114-035439","article-title":"Angiogenesis and Eye Disease","volume":"1","author":"Usui","year":"2015","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/nature04482","article-title":"Retinal Angiogenesis in Development and Disease","volume":"438","author":"Gariano","year":"2005","journal-title":"Nature"},{"key":"ref_3","first-page":"1381","article-title":"Terms Non-exudative and Non-neovascular: Awaiting Entry at the Doors of AMD Reclassification. Graefe\u2019s Arch","volume":"259","author":"Sharma","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.3389\/fnins.2019.01172","article-title":"Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy","volume":"13","author":"Rossino","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1442-9071.2011.02713.x","article-title":"Central Retinal Vein Occlusion: A Review","volume":"40","author":"McAllister","year":"2012","journal-title":"Clin. Experiment. Ophthalmol."},{"key":"ref_6","first-page":"19","article-title":"Retinal Diseases and VISION 2020","volume":"16","author":"Yorston","year":"2003","journal-title":"Community Eye Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1107295","DOI":"10.3389\/fimmu.2023.1107295","article-title":"Proteomics Profiling of Vitreous Humor Reveals Complement and Coagulation Components, Adhesion Factors, and Neurodegeneration Markers as Discriminatory Biomarkers of Vitreoretinal Eye Diseases","volume":"14","author":"Santos","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Santos, F.M., Mesquita, J., Castro-de-Sousa, J.P., Ciordia, S., Paradela, A., and Tomaz, C.T. (2022). Vitreous Humor Proteome: Targeting Oxidative Stress, Inflammation, and Neurodegeneration in Vitreoretinal Diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11030505"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jadeja, R.N., and Martin, P.M. (2021). Oxidative Stress and Inflammation in Retinal Degeneration. Antioxidants, 10.","DOI":"10.3390\/antiox10050790"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.visres.2017.06.015","article-title":"Novel Therapeutic Targets in Diabetic Macular Edema: Beyond VEGF","volume":"139","author":"Urias","year":"2017","journal-title":"Vision Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/08977194.2018.1477140","article-title":"Evaluation of the Growth Factors VEGF-A and VEGF-B in the Vitreous and Serum of Patients with Macular and Retinal Vascular Diseases","volume":"36","author":"Mesquita","year":"2018","journal-title":"Growth Factors"},{"key":"ref_12","first-page":"281981","article-title":"Nonsteroidal Anti-Inflammatory Drugs for Retinal Disease","volume":"2013","author":"Schoenberger","year":"2013","journal-title":"Int. J. Inflam."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.7150\/thno\/v01p0395","article-title":"Lasting Controversy on Ranibizumab and Bevacizumab","volume":"1","author":"Zou","year":"2012","journal-title":"Theranostics"},{"key":"ref_14","first-page":"413","article-title":"A Review of Aflibercept Treatment for Macular Disease Ophthalmol","volume":"10","author":"Anguita","year":"2021","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, Durability, and Safety of Intravitreal Faricimab Up to Every 16 Weeks for Neovascular Age-related Macular Degeneration (Tenaya and Lucerne): Two Randomised, Double-masked, Phase 3, Non-inferiority Trials","volume":"399","author":"Heier","year":"2022","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.2147\/OPTH.S318026","article-title":"Guidelines for the Management of Center-Involving Diabetic Macular Edema: Treatment Options and Patient Monitorization","volume":"15","author":"Figueira","year":"2021","journal-title":"Clin. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Iturriaga-Goyon, E., Buentello-Volante, B., Maga\u00f1a-Guerrero, F.S., and Garfias, Y. (2021). Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis. Cells, 10.","DOI":"10.3390\/cells10061455"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/nat.2015.0573","article-title":"Fit for the Eye: Aptamers in Ocular Disorders","volume":"26","author":"Drolet","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.addr.2018.08.006","article-title":"Therapeutic Aptamers in Discovery, Preclinical and Clinical Stages","volume":"134","author":"Ismail","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrd1955","article-title":"Pegaptanib, a Targeted Anti-VEGF Aptamer for Ocular Vascular Disease","volume":"5","author":"Ng","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","unstructured":"(2022, April 27). Phase 2A Open Label Safety Study of Fovista\u00ae (Anti-PDGF BB) Regimen Administered in Combination With Anti-VEGF Therapy to Study Sub-Retinal Fibrosis in Neovascular AMD-Full Text View-ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02214628?term=Fovista&phase=01&draw=2&rank=1."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ophtha.2015.09.004","article-title":"A Phase 1 Study of Intravitreous E10030 in Combination with Ranibizumab in Neovascular Age-Related Macular Degeneration","volume":"123","author":"Jaffe","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_23","unstructured":"(2022, April 27). A Phase 3 Safety and Efficacy Study of Fovista\u00ae (E10030) Intravitreous Administration in Combination With Lucentis\u00ae Compared to Lucentis\u00ae Monotherapy-Study Results-ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT01940900."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lfs.2017.07.025","article-title":"New Perspectives of Physiological and Pathological Functions of Nucleolin (NCL)","volume":"186","author":"Jia","year":"2017","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1182\/blood-2005-07-2961","article-title":"The Angiogenic Function of Nucleolin is Mediated by Vascular Endothelial Growth Factor and Nonmuscle Myosin","volume":"107","author":"Huang","year":"2006","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/j.drudis.2019.06.018","article-title":"Nucleolin-based Targeting Strategies for Cancer Therapy: From Targeted Drug Delivery to Cytotoxic Ligands","volume":"24","author":"Romano","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.exer.2015.09.005","article-title":"Topical Application of a G-Quartet Aptamer Targeting Nucleolin Attenuates Choroidal Neovascularization in a model of age-related macular degeneration","volume":"140","author":"Leaderer","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Iturriaga-Goyon, E., Vivanco-Rojas, O., Maga\u00f1a-Guerrero, F.S., Buentello-Volante, B., Castro-Salas, I., Aguayo-Flores, J.S., Gracia-Mora, I., Rivera-Huerta, M., S\u00e1nchez-Bart\u00e9s, F., and Garfias, Y. (2021). As1411 Nucleolin-specific Binding Aptamers Reduce Pathological Angiogenesis Through Inhibition of Nucleolin Phosphorylation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313150"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Miranda, A., Santos, T., Largy, E., and Cruz, C. (2021). Locking up the AS1411 Aptamer with a Flanking Duplex: Towards an Improved Nucleolin-Targeting. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020121"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114208","DOI":"10.1016\/j.bcp.2020.114208","article-title":"Recognition of Nucleolin Through Interaction with RNA G-quadruplex","volume":"189","author":"Santos","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7487","DOI":"10.1093\/nar\/gkx274","article-title":"\u201cG-quadruplex Structure of an Anti-proliferative DNA Sequence,\u201d","volume":"45","author":"Do","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moreira, D., Leit\u00e3o, D., Lopes-Nunes, J., Santos, T., Figueiredo, J., Miranda, A., Alexandre, D., Tomaz, C., Mergny, J.L., and Cruz, C. (2022). G-Quadruplex Aptamer-Ligand Characterization. Molecules, 27.","DOI":"10.3390\/molecules27206781"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1039\/C9OB00318E","article-title":"Aptamer-Guided Acridine Derivatives for Cervical Cancer","volume":"17","author":"Carvalho","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/IAE.0000000000002196","article-title":"Dexamethasone Implant for Diabetic Macular Edema in Naive Compared with Refractory Eyes: The International Retina Group Real-life 24-month Multicenter Study. The Irgrel-dex Study","volume":"39","author":"Iglicki","year":"2019","journal-title":"Retina"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.biochi.2015.06.002","article-title":"Assessment of Selectivity of G-quadruplex Ligands Via an Optimised FRET Melting Assay","volume":"115","author":"Rache","year":"2015","journal-title":"Biochimie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/cmdc.201600511","article-title":"Design, Synthesis, and Evaluation of 2,9-Bis[(substituted-aaminomethyl)phenyl]-1,10-phenanthroline Derivatives as G-Quadruplex Ligands","volume":"12","author":"Gueddouda","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_37","first-page":"367","article-title":"Synergistic Stimulatory Effect of Glucocorticoid, EGF and Insulin on the Synthesis of Ribosomal RNA and Phosphorylation of Nucleolin in Primary Cultured Rat Hepatocytes","volume":"1092","author":"Suzuki","year":"1991","journal-title":"BBA Mol. Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1039\/c3tb20412j","article-title":"Selective Delivery of an Anticancer Drug with Aptamer-functionalized Liposomes to Breast Cancer Cells In Vitro and In Vivo","volume":"1","author":"Xing","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_39","first-page":"1172","article-title":"Anti-HER2 Immunoliposomes: Enhanced Efficacy an Attributable to Targeted Delivery","volume":"8","author":"Park","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120571","DOI":"10.1016\/j.ijpharm.2021.120571","article-title":"Design of liposomes as drug delivery system for therapeutic applications","volume":"601","author":"Nogueira","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0959-440X(99)80041-4","article-title":"Multistranded DNA Structures","volume":"9","author":"Gilbert","year":"1999","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ymeth.2012.05.003","article-title":"NMR Spectroscopy of G-quadruplexes","volume":"57","author":"Adrian","year":"2012","journal-title":"Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8112","DOI":"10.1021\/bi00150a002","article-title":"Guanine Residues in d(T2AG3) and d(T2G4) Form Parallel-Stranded Potassium Cation Stabilized G-quadruplexes with Anti Glycosidic Torsion Angles in Solution","volume":"35","author":"Wang","year":"1992","journal-title":"Biochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lombardo, D., and Kiselev, M.A. (2022). Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030543"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/08982100601186508","article-title":"Environmental Scanning Electron Microscopy Offers Real-Time Morphological Analysis of Liposomes and Niosomes","volume":"17","author":"Perrie","year":"2007","journal-title":"J. Liposome Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ijpharm.2010.12.021","article-title":"Microscopy imaging of liposomes: From coverslips to environmental SEM","volume":"417","author":"Bibi","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ijbiomac.2019.10.256","article-title":"Chitosan Coated Liposomes (CCL) Containing Triamcinolone Acetonide for Sustained Delivery: A Potential Topical Treatment for Posterior Segment Diseases","volume":"143","author":"Khalil","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12951-019-0498-7","article-title":"Liposomes for Effective Drug Delivery to the Ocular Posterior Chamber","volume":"17","author":"Lai","year":"2019","journal-title":"J. Nanobiotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2015.00286","article-title":"Advances and Challenges of Liposome Assisted Drug Delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/jcb.22643","article-title":"Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma","volume":"110","author":"Joo","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"J. Microsc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102429","DOI":"10.1016\/j.nano.2021.102429","article-title":"Nanoaggregate-forming lipid-conjugated AS1411 aptamer as a promising tumor-targeted delivery system of anticancer agents in vitro","volume":"36","author":"Carvalho","year":"2021","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lopes-Nunes, J., Agonia, A.S., Rosado, T., Gallardo, E., Palmeira-de-Oliveira, R., Palmeira-de-Oliveira, A., Martinez-de-Oliveira, J., Fonseca-Moutinho, J., Campello, M.P.C., and Paiva, A. (2021). Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells. Cancers, 13.","DOI":"10.3390\/cancers13164038"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"42544","DOI":"10.1038\/srep42544","article-title":"Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA","volume":"7","author":"Pereira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1002\/bit.24558","article-title":"AS1411 Aptamer Tagged PLGA-Lecithin-PEG Nanoparticles for Tumor Cell Targeting and Drug Delivery","volume":"109","author":"Aravind","year":"2012","journal-title":"Biotechnol. Bioeng."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:35:49Z","timestamp":1760124949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ph16050751"],"URL":"https:\/\/doi.org\/10.3390\/ph16050751","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,16]]}}}