Biomedicine & Pharmacotherapy最新文献

{"title":"Emerging role of the cardiac lipidome in the progression of heart failure","authors":"Lorenzo Flori ,&nbsp;Vincenzo Calderone ,&nbsp;Lara Testai","doi":"10.1016/j.biopha.2025.118385","DOIUrl":"10.1016/j.biopha.2025.118385","url":null,"abstract":"<div><div>Lipids play structural and cellular functions, being a part of cellular membranes, regulating signaling, transmembrane transporters and energy depots. The lipid profile is not static, and a large number of human pathologies have been linked to alterations of lipid homeostasis, including cancer, neurodegenerative, cardiovascular and metabolic diseases. Among the cardiovascular diseases, an altered lipid metabolism has been implicated in heart failure (HF). Based on the recent evidence, changes in the levels of some specific lipids reflect the progression of cardiovascular diseases and, interestingly, their alterations can also occur independently from obesogenic stimuli. In this review, evidence of lipotoxicity at cardiac level will be reported discriminating between clinical or preclinical evidence and the presence or absence of obesogenic conditions. In numerous experimental models, both with and without obesity, ceramides (CERs) and triacyclglycerols (TAGs) levels increased at the cardiac level and were associated with a higher risk of cardiovascular diseases and directly correlated with their severity. Conversely, cardiolipin (CL), the peculiar phospholipid of the inner mitochondrial membrane, is inversely related to cardiovascular risk, and it is considered a crucial factor responsible for the regulation of mitochondrial function and therefore useful as an early marker of prodromal changes driving the cardiac contractility alterations. Most of the progress in this field has probably focused on this lipid: aimed at the development of synthetic analogues useful for mimicking the role of CLs, in order to restore its physiological function; but also, to the discovery of compounds capable of specifically bind CL, useful as diagnostic tools.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118385"},"PeriodicalIF":7.5,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcoplasmic reticulum-mitochondrial calcium communication: A new target for cardiovascular therapy","authors":"Juan Wang ,&nbsp;Shaorui Li ,&nbsp;Chenghao Yu ,&nbsp;Ying Wang ,&nbsp;Shaojun Xu ,&nbsp;Yuduan Wang ,&nbsp;Le Zhao ,&nbsp;Jinyan Zhang","doi":"10.1016/j.biopha.2025.118424","DOIUrl":"10.1016/j.biopha.2025.118424","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) remains a leading cause of mortality and disability globally. Various cardiovascular diseases are often associated with ion dyshomeostasis within and outside cardiomyocytes, such as sodium ions, calcium ions and potassium ions. Calcium ions (Ca^2 +) not only participate in the contractile activity of cardiomyocytes and smooth muscle cells, but also participate in the tricarboxylic acid cycle as a cellular energy source, and act as a second messengers during many biological processes. Consequently, the concentration of calcium ions inside and outside the cell, as well as the distribution of calcium ions in various organelles and the cytoplasm are critical. Sarcoplasmic reticulum (SR)-mitochondrial calcium communication plays a crucial role in the distribution of Ca²⁺ in the cytoplasm and organelles. Disturbed calcium signaling caused by impaired calcium communication between the sarcoplasmic reticulum and mitochondria may play a significant role in the pathogenesis of cardiovascular diseases. Recent studies have increasingly demonstrated the significant role of SR-mitochondrial calcium communication in the progression of cardiovascular diseases, suggesting its potential as a therapeutic target. This review provides a summary of existing evidence supporting the contribution of SR-mitochondrial calcium communication disorders to the development of CVD, emphasizing its potential as a promising therapeutic target for CVD management.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118424"},"PeriodicalIF":7.5,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of inducible damage-associated molecular patterns after interleukin-12 gene electrotransfer in mouse melanoma and colorectal cell lines","authors":"Ajda Medved ,&nbsp;Masa Omerzel ,&nbsp;Tanja Jesenko ,&nbsp;Simon Bucek ,&nbsp;Gregor Sersa ,&nbsp;Maja Cemazar","doi":"10.1016/j.biopha.2025.118414","DOIUrl":"10.1016/j.biopha.2025.118414","url":null,"abstract":"<div><div>Interleukin-12 (IL-12) has demonstrated potent antitumor effects by activating natural killer (NK) and T cells, but its systemic administration poses challenges due to toxicity. This study investigated gene electrotransfer (GET) as a localized delivery method for IL-12 plasmids in B16F10 and CT26 tumor cells and its effect on the expression of damage-associated molecular patterns (DAMPs) and several cytokines. We observed the activation of cytosolic sensors and cytokine production, with the expression of IL-6 and TNF-α upregulated only after IL-12 GET, suggesting the involvement of inducible damage-associated molecular patterns (iDAMPs) in the immune response to IL-12 gene therapy. These findings highlight the multifaceted immune activation triggered by GET, offering insights for improving IL-12-based cancer therapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118414"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines, chemokines, and immune cells involved in oral immunity towards the dental cariogenic bacterium Streptococcus mutans: Therapeutic interventions and vaccination","authors":"Mohammadreza Taghipour Kazerooni ,&nbsp;Shiva Hemmati","doi":"10.1016/j.biopha.2025.118394","DOIUrl":"10.1016/j.biopha.2025.118394","url":null,"abstract":"<div><div>Untreated dental caries, or tooth decay, is the most frequent health-related affliction, mainly due to insufficient service in low- and middle-income countries. The inflammatory niche in the presence of <em>Streptococcus mutans</em> and its biofilm in the oral cavity can lead to immune-mediated tissue injury, enamel demineralization, cavitation, pulp infection, dental loss, and extraoral disorders such as endocarditis. Recruiting immune responses to fight pathogens is a novel therapeutic strategy that prevents antimicrobial resistance and regulates the immune microenvironment. Within this manuscript, the host’s determinative innate and adaptive immune functions in the progression or regression of dental caries are introduced. Primarily, the correlation of <em>S. mutans</em> and its virulence factors, such as antigenI/II, quorum-sensing peptides, collagen-binding proteins, glucosyltransferases, and lipoteichoic acid on oral immunopathology has been classified. The role of phagocytosis, NETosis, and pyroptosis on pathogen clearance and the effect of virulence factors on the immune markers in the secretome of dendritic cells, dental pulp stem cells, and odontoblasts are described. The placement of natural products, antimicrobial peptides, probiotics, stem cells, nanoparticles, and irradiation involved in the immunotherapy of dental caries is investigated. The nasopharynx-associated lymphoid tissue in mucosal administration of the anti-caries vaccine is critical. Therefore, the effects of immunodominant antigens, delivery vectors, promoters, endogenous inhibitory microRNAs, the prime-boost vaccination strategy, and co-immunization of genetic vaccines with cytokines and chemokines as adjuvants on immunocyte activation, salivary IgA, and specific serum IgG in caries prevention are determined. Conclusively, successful therapeutic interventions that recruit oral immunity to eradicate <em>S. mutans</em> affected ERK/MAPK, NF-κB, and inflammasome signaling pathways in favor of Th1 response suppression. The most effective caries preventive vaccines produced a combination of Th1, Th2, and Th17 responses. Finally, multivalent vaccines inhibiting the activation of suppressor of cytokine signaling (<em>SOCS</em>) genes are proposed for the successful development of anti-caries vaccine.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118394"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-specific response of visceral adipocytes differentiated from human adipose-derived mesenchymal stem cells to branched-chain alpha-keto acid (BCKA) dehydrogenase activation","authors":"Elżbieta Supruniuk ,&nbsp;Agnieszka Mikłosz ,&nbsp;Bartłomiej Łukaszuk ,&nbsp;Marcin Baranowski ,&nbsp;Adam Paszko ,&nbsp;Łukasz Szczerbiński ,&nbsp;Kamil Grubczak ,&nbsp;Aleksandra Starosz ,&nbsp;Adrian Chabowski","doi":"10.1016/j.biopha.2025.118426","DOIUrl":"10.1016/j.biopha.2025.118426","url":null,"abstract":"<div><h3>Aims</h3><div>The causal role of branched-chain amino acids (BCAAs) and their transamination derivatives (branched-chain α-ketoacids, BCKAs) was observed in the progression of obesity and its metabolic complications. In the study, we aimed to stimulate BCAA catabolic flux with an inhibitor of BCKA dehydrogenase kinase (i.e., BT2) to explore metabolic consequences using visceral ADMSCs, obtained from non-obese men and men with obesity, and differentiated to adipocytes.</div></div><div><h3>Materials and Methods</h3><div>ADMSCs metabolism was assessed using real-time PCR, Western Blot, Ultra-High Performance Liquid Chromatography, Gas-Liquid Chromatography, Seahorse analysis, liquid scintillation counting, flow cytometry, immunofluorescence and spectrophotometric assays.</div></div><div><h3>Results</h3><div>We report that obesity was associated with the redistribution of fatty acid transporters among a higher number of adipocytes (higher number of CD36/SR-B2 and FATP4 positive cells), but at the same time lowered surface abundance of transporters per cell (CD36/SR-B2, FATP1, FATP4, FABPpm). Despite that, the metabolic consequences of BT2 administration were strictly associated with the donor-specific inherent cellular properties, what enabled a differentiation of two adipocyte subpopulations with low and high metabolic activity. BT2 effects were more profound in the latter group, wherein pro-lipolytic and β-oxidation-related markers were upregulated, including higher ATP production, glycerol release and acid-soluble metabolites accumulation, reduced fatty acid synthase expression, decreased free fatty acids and triacylglycerols concentrations.</div></div><div><h3>Conclusions</h3><div>Our data highlight the substantial contribution of BCAA catabolism in adipocyte lipogenesis, and effective utilization of energy substrates. The more efficient the regulation of fat storage in the adipocytes, the less would be the lipotoxic effects in non-adipose tissues.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118426"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatin (STRN): A multifunctional protein in cardiovascular health and cancer progression","authors":"Shadi Khadijeh Gholami ,&nbsp;Anupa Sivakumar ,&nbsp;Jaiprakash Mohanraj ,&nbsp;Reyhaneh Farghadani ,&nbsp;Sofiah Hanis Ahmad Hisham ,&nbsp;Mahyar Heydarpour ,&nbsp;Gordon H. Williams","doi":"10.1016/j.biopha.2025.118395","DOIUrl":"10.1016/j.biopha.2025.118395","url":null,"abstract":"<div><div>Striatin (STRN) is a multifunctional scaffold protein that has emerged as a key regulator in both cardiovascular disease (CVD) and cancer. Through modulation of kinases, phosphatases, and calcium-dependent pathways, STRN plays a pivotal role in maintaining cell signaling. In CVDs, STRN role is mediated via STRN influence on vascular reactivity, blood pressure regulation, and vascular remodeling. Moreover, STRN polymorphism has been linked to salt sensitivity of blood pressure. At the same time, the STRN role in tumor progression has been documented across multiple cancers, primarily through its fusion with proteins such as anaplastic lymphoma kinase (ALK), or increased STRN expression. The STRN-ALK fusion has been documented to drive oncogenesis in lung, thyroid, and several other cancers. This review synthesizes current findings on the STRN dual role in cardio-oncology, highlighting its molecular mechanisms and potential therapeutic implications. However, additional research is required for a deeper understanding of STRN-mediated signaling, which may lead to the development of novel biomarkers for interventions in cardio-oncology.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118395"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbonic anhydrases inhibition in the management of cardiovascular and cardiometabolic disorders","authors":"Alice Mallia,&nbsp;Lisa Brocca,&nbsp;Giulia G. Papaianni,&nbsp;Cristina Banfi","doi":"10.1016/j.biopha.2025.118396","DOIUrl":"10.1016/j.biopha.2025.118396","url":null,"abstract":"<div><div>Carbonic anhydrases are a family of zinc-metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and hydrogen ions. In mammals, there are 16 different α-carbonic anhydrases isoforms that vary in their catalytic activity, subcellular localization, and tissue distribution. The role of this class of enzymes has been known since their discovery, but their involvement in the pathogenesis and progression of cardiovascular and cardiometabolic diseases remains an area with a wide scope of exploration. Many studies investigated the role that carbonic anhydrases play in the development of heart failure, vascular calcification, myocardial infarction, diabetes and obesity, and how the use of carbonic anhydrases inhibitors may be beneficial in managing these conditions. Clinical trials have been designed to investigate the beneficial role of the carbonic anhydrases inhibitor acetazolamide in combination with loop diuretics in the treatment of patients with acute decompensate heart failure with volume overload. This review discusses the role of carbonic anhydrases in cardiovascular and cardiometabolic diseases, exploring their catalytic activity, subcellular localization, and tissue distribution and highlights the potential use of carbonic anhydrases inhibitors in managing cardiovascular and cardiometabolic disorders. The involvement of carbonic anhydrases in the development of cardiovascular pathologies is an area for further exploration, with potential implications for targeted treatments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118396"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical review of in vitro and in vivo biomedical applications of gold nanoparticles: From toxicology to cancer therapy","authors":"Ilyas Ozcicek","doi":"10.1016/j.biopha.2025.118410","DOIUrl":"10.1016/j.biopha.2025.118410","url":null,"abstract":"<div><div>Due to their unique and fascinating physicochemical properties, gold nanoparticles (AuNPs) are frequently used in the biomedical field including drug delivery, cancer therapy, biosensor, bioimaging, gene therapy, tissue engineering and antibacterial applications. Their superior properties such as high biocompatibility with living organisms, stability, SPR properties, small size, large surface area, adjustable stability, easy synthesizability and surface modification have increased the success of AuNPs in nanomedicine applications. AuNPs, which can be synthesized by many methods, can be easily adjusted in size and shape. Various mechanisms are being proposed to increase the affinity of functional group-bearing AuNPs to biomolecules and turn them into effective drug delivery systems with improved specificity. Among other metallic nanoparticles, AuNPs have great potential to be used in bio-imaging field. Considering the superior properties of AuNPs and controllable interactions with different biomolecules, AuNPs can be used as biosensor platforms in various diagnostic processes. This review article will be focused on the recent advances in various biomedical applications of AuNPs including toxicity, cancer therapy, drug delivery, gene silencing, bio-imaging, tissue engineering, diagnostic applications, and antibacterial studies. It is concluded that clinical studies on AuNPs with expanded strategies will be witnessed in the coming years.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118410"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transcriptional factor Neurod1 regulates preconditioned-induced neurogenesis by activating sodium/calcium exchanger NCX1 in ischemic rats","authors":"Ornella Cuomo ,&nbsp;Viviana Viscardi ,&nbsp;Paola Brancaccio ,&nbsp;Serenella Anzilotti ,&nbsp;Natascia Guida ,&nbsp;Giovanna Lombardi ,&nbsp;Luigi Formisano ,&nbsp;Rodolfo Esposito ,&nbsp;Antonio Vinciguerra ,&nbsp;Mario Campanile ,&nbsp;Lucia D.’Esposito ,&nbsp;Lucio Annunziato ,&nbsp;Giuseppe Pignataro","doi":"10.1016/j.biopha.2025.118401","DOIUrl":"10.1016/j.biopha.2025.118401","url":null,"abstract":"<div><div>Over the last two decades, there has been an increasing interest in understanding the mechanisms underlying neurogenesis as potential neurorestorative strategy triggered by ischemic preconditioning (IPC). Among these mechanisms, neuronal calcium homeostasis plays a fundamental role in supporting neurogenesis. Since sodium/calcium exchangers NCX1 and NCX3 are key effectors of IPC-mediated neuroprotection, this study aimed to investigate their contribution to the activation and maintenance of endogenous neurogenesis induced by IPC. Specifically, in an adult rat model of ischemic preconditioning, we examined whether: (1) IPC+tMCAO modulates the neurogenesis through NCX1 and NCX3 activation in subventricular zone (SVZ) and in the ipsilateral striatum; (2) NCX1 and NCX3 silencing may modulate the expression of “immature” neurons expressing the transcriptional factor NeuroD1 in SVZ; (3) the effects of IPC+tMCAO on the two isoforms, NCX1 and NCX3, are mediated by the transcriptional factor NeuroD1 expressed by “immature” neurons; (4) NeuroD1 directly binds ncx promoter evaluated by luciferase assay. Our findings revealed that, in the SVZ, IPC+tMCAO enhances at the same time either the expression of the neurogenesis marker, NeuroD1, and the expression of NCX1 and NCX3. Furthermore, the silencing of both NCX1 or NCX3 not only abolished the protective effects of IPC+tMCAO, but also impaired neuroblast proliferation, as NeuroD1 upregulation was completely suppressed. More interestingly, NeuroD1 directly binds ncx1 promoter, thus increasing its expression. Collectively, these results demonstrated that the transcriptional factor NeuroD1 regulates IPC+tMCAO-induced neurogenesis in the subventricular zone and in striatum by activating sodium/calcium exchanger ncx1, but not ncx3, in ischemic rats.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118401"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24)","authors":"Cindy Mendes ,&nbsp;Filipa Martins ,&nbsp;Sara Granja ,&nbsp;Joana Gonçalves ,&nbsp;Hélio Barros ,&nbsp;Teresa Casimiro ,&nbsp;Ana Aguiar-Ricardo ,&nbsp;Fernanda Silva ,&nbsp;Bruna Abreu ,&nbsp;Miguel Cristovão ,&nbsp;Saudade André ,&nbsp;Sofia A. Pereira ,&nbsp;Fátima Baltazar ,&nbsp;Helena Cabral-Marques ,&nbsp;Maria Manuela Gaspar ,&nbsp;Luís G. Gonçalves ,&nbsp;Vasco D.B. Bonifácio ,&nbsp;Jacinta Serpa","doi":"10.1016/j.biopha.2025.118405","DOIUrl":"10.1016/j.biopha.2025.118405","url":null,"abstract":"<div><div>Lung 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_G4-LA₂₄), the nanoformulation SeChry@PURE_G4-LA₂₄, in NSCLC. We explored the impact of SeChry nanoformulation on cell death mechanisms, including ferroptosis, and its influence on angiogenesis in <em>in vitro</em> and <em>in vivo</em> models. SeChry@PURE_G4-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@PURE_G4-LA₂₄ administration. These findings suggest the potential of SeChry@PURE_G4-LA₂₄ as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118405"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}