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Metabolism-Targeted Therapy in NSCLC - A New Theranostics Inhalation Approach Using Lactate Functionalized and Selenium-Chrysin Loaded Nanoparticles (SeChry@PURE-LA).

2025-09Text Open access
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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.date.accessioned2025-08-26T14:06:01Z
dc.date.available2025-08-26T14:06:01Z
dc.date.issued2025-09
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 (PURE-LA), the nanoformulation SeChry@PURE-LA, 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@PURE-LA 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@PURE-LA administration. These findings suggest the potential of SeChry@PURE-LA as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.
dc.identifier.citationBiomed Pharmacother. 2025; 190:118405
dc.identifier.doi10.1016/j.biopha.2025.118405
dc.identifier.other40752426
dc.identifier.urihttp://hdl.handle.net/10400.17/5146
dc.language.isoen
dc.peerreviewedyes
dc.publisherElsevier
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectFourth-generation polyurea dendrimer functionalized with lactic acid (PURE(G4)-LA(24))
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.subjectHSJ ANPAT
dc.titleMetabolism-Targeted Therapy in NSCLC - A New Theranostics Inhalation Approach Using Lactate Functionalized and Selenium-Chrysin Loaded Nanoparticles (SeChry@PURE-LA).
dc.typetext
dspace.entity.typePublication
oaire.citation.startPage118405
oaire.citation.volume190
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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