{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:57Z","timestamp":1788930537553,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["COMPETE2030"],"award-info":[{"award-number":["COMPETE2030"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["Centro 2030"],"award-info":[{"award-number":["Centro 2030"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"award":["COMPETE2030"],"award-info":[{"award-number":["COMPETE2030"]}],"id":[{"id":"https:\/\/ror.org\/01rkhv978","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Centro 2030"],"award-info":[{"award-number":["Centro 2030"]}],"id":[{"id":"https:\/\/ror.org\/01rkhv978","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Projeto financiado pela Bolsa de Investiga\u00e7\u00e3o em Oncologia do N\u00facleo Regional do Centro da Liga Portuguesa Contra o Cancro"},{"id":[{"id":"https:\/\/ror.org\/03r31ar10","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Portuguese NMR Network","award":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"]}]},{"name":"national funds"},{"name":"EATRIS"},{"name":"FCT","award":["UID\/06397\/2025"],"award-info":[{"award-number":["UID\/06397\/2025"]}]},{"name":"FCT","award":["UID\/PRR\/06397\/2025"],"award-info":[{"award-number":["UID\/PRR\/06397\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aptamer-functionalized liposomes are a promising strategy to improve the selectivity of anticancer therapies. AT11-L2 is a G-quadruplex (G4)-forming aptamer with high affinity for nucleolin (NCL), which is overexpressed at the surface of non-small cell lung cancer (NSCLC) cells. Here, we developed AT11-L2-functionalized liposomes loaded with doxorubicin (DOX) or BRACO-19 for targeted delivery to NSCLC cells. The effects of both compounds on AT11-L2 stability and the ability of the aptamer to retain G4 folding after liposome conjugation were evaluated. Liposomes were characterized for size, polydispersity, surface charge, stability, encapsulation efficiency, and release profile. Biological activity was assessed in A549 and MRC-5 cells. Liposomes had an average size of approximately 110 nm, with a slight size increase and reduced surface charge after AT11-L2 functionalization. The aptamer retained G4 folding in 100 mM KCl after conjugation. Encapsulation efficiency was approximately 90%. DOX showed substantial release within 72 h, whereas BRACO-19 exhibited a more sustained profile. AT11-L2-DOX liposomes showed preferential effects in A549 cells, while BRACO-19 formulations displayed lower selectivity and cytotoxicity. Additionally, the NCL-dependent internalization of AT11-L2-functionalized liposomes was supported by a protein-blocking assay using an anti-NCL antibody. These results support AT11-L2-functionalized liposomes as a versatile NCL-targeted delivery system for NSCLC.<\/jats:p>","DOI":"10.3390\/molecules31173134","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"3134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aptamer-Functionalized Liposomes for Targeted Delivery of Anticancer Drugs in Lung Cancer"],"prefix":"10.3390","volume":"31","author":[{"given":"Daniela","family":"Leit\u00e3o","sequence":"first","affiliation":[{"name":"RISE-Health UBI, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-3310","authenticated-orcid":false,"given":"David","family":"Moreira","sequence":"additional","affiliation":[{"name":"RISE-Health UBI, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"J\u00e9ssica","family":"Lopes-Nunes","sequence":"additional","affiliation":[{"name":"RISE-Health UBI, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Joana","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"RISE-Health UBI, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-1242","authenticated-orcid":false,"given":"Carla","family":"Cruz","sequence":"additional","affiliation":[{"name":"RISE-Health UBI, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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