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Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24)

2025-09Artigo científico Acesso aberto
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dc.contributor.authorMendes, Cindy
dc.contributor.authorMartins, Filipa
dc.contributor.authorGranja, Sara
dc.contributor.authorGonçalves, Joana
dc.contributor.authorBarros, Hélio
dc.contributor.authorCasimiro, Teresa
dc.contributor.authorAguiar-Ricardo, Ana
dc.contributor.authorSilva, Fernanda
dc.contributor.authorAbreu, Bruna
dc.contributor.authorCristovão, Miguel
dc.contributor.authorAndré, Saudade
dc.contributor.authorPereira, Sofia A.
dc.contributor.authorBaltazar, Fátima
dc.contributor.authorCabral-Marques, Helena
dc.contributor.authorGaspar, Maria Manuela
dc.contributor.authorGonçalves, Luís G.
dc.contributor.authorBonifácio, Vasco D. B.
dc.contributor.authorSerpa, Jacinta
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionLAQV@REQUIMTE
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)
dc.contributor.pblElsevier
dc.date.accessioned2025-09-03T21:59:29Z
dc.date.available2025-09-03T21:59:29Z
dc.date.issued2025-09
dc.descriptionFunding Information: The institutions are funded by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNO-VA4Health (UIDB/04462/2020 and UIDP/04462/2020), to MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020) and the Associated Laboratory LS4FUTURE (LA/P/0087/2020). During the course of PhD, Cindy Mendes was funded by Liga Portuguesa Contra o Cancro –Nucleo regional Sul (LPCC-NRS) and by an FCT individual Ph.D. fellowship (2020.06956.BD). Isabel Lemos was funded by an FCT individual Ph.D. fellowship (UI/BD/154203/2022). Ana Hipólito was funded by a FCT individual Ph.D. fellowship (SFRH/BD/148441/2019). Filipa Martins was funded by a FCT individual Ph.D. fellowship (2020.04780.BD). Luis G. Gonçalves was financed by a FCT contract according to DL57/2016, [SFRH/BPD/111100/2015]. This work benefited from access to CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. Publisher Copyright: © 2025 The Authors
dc.description.abstractLung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and tissue damage, and contributing to various pathophysiological changes. This study aimed to investigate the therapeutic potential of selenium–chrysin (SeChry), a cysteine metabolism inhibitor, and its delivery targeted at MCT1 by encapsulation in fourth-generation polyurea dendrimers functionalized with lactic acid (PUREG4-LA24), the nanoformulation SeChry@PUREG4-LA24, in NSCLC. We explored the impact of SeChry nanoformulation on cell death mechanisms, including ferroptosis, and its influence on angiogenesis in in vitro and in vivo models. SeChry@PUREG4-LA24 induces cell death through the induction of intracellular ROS and lipid peroxides, resulting in distinct expression patterns of ferroptosis-associated genes across cell lines. Experiments using chicken embryo chorioallantoic membrane (CAM) and mouse orthotopic xenograft models revealed a trend toward decreased tumor growth and angiogenesis with SeChry@PUREG4-LA24 administration. These findings suggest the potential of SeChry@PUREG4-LA24 as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent19
dc.format.extent10960920
dc.identifier.doi10.1016/j.biopha.2025.118405
dc.identifier.issn0753-3322
dc.identifier.otherPURE: 128620998
dc.identifier.otherPURE UUID: cbc7eaa7-3688-4071-8d15-14cdd9247e17
dc.identifier.otherScopus: 105012146221
dc.identifier.otherPubMed: 40752426
dc.identifier.otherORCID: /0000-0001-5683-3552/work/191132402
dc.identifier.otherORCID: /0000-0002-8456-9995/work/191132528
dc.identifier.otherORCID: /0000-0002-2193-1440/work/191132660
dc.identifier.otherORCID: /0000-0002-1548-5907/work/191132899
dc.identifier.otherORCID: /0000-0001-9405-6221/work/207947354
dc.identifier.urihttp://hdl.handle.net/10362/187507
dc.identifier.urlhttps://www.scopus.com/pages/publications/105012146221
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04462%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04462%2F2020/PT
dc.relationiNOVA4Health - Programme in Translational Medicine (iBET, CEDOC/FCM, IPOLFG e ITQB)
dc.relationinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04612%2F2020/PT
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dc.relationinfo:eu-repo/grantAgreement/FCT//UI%2FBD%2F154203%2F2022/PT
dc.relationinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F148441%2F2019/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/OE/2020.04780.BD/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F111100%2F2015/PT
dc.subjectFourth-generation polyurea dendrimer functionalized with lactic acid (PUREG4-LA24)
dc.subjectMetabolic remodeling
dc.subjectMetabolism-directed therapy
dc.subjectNon-small-cell lung carcinoma (NSCLC)
dc.subjectOxidative stress-induced ferroptosis
dc.subjectReactive oxygen species (ROS)
dc.subjectSelenium-containing chrysin (SeChry)
dc.subjectPharmacology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMetabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24)en
dc.typejournal article
degois.publication.firstPage1
degois.publication.lastPage19
degois.publication.titleBiomedicine and Pharmacotherapy
degois.publication.volume190
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oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
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