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

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 (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.

Palavras-chave

Non-small-cell lung carcinoma (NSCLC) Metabolic remodeling Selenium-containing chrysin (SeChry) Fourth-generation polyurea dendrimer functionalized with lactic acid (PUREG4-LA24) Reactive oxygen species (ROS) Oxidative stress-induced ferroptosis Metabolism-directed therapy

URI

http://hdl.handle.net/10400.22/31537

Citação

Mendes, C., Martins, F., Granja, S., Gonçalves, J., Barros, H., Casimiro, T., Aguiar-Ricardo, A., Silva, F., Abreu, B., Cristovão, M., André, S., Pereira, S. A., Baltazar, F., Cabral-Marques, H., Gaspar, M. M., Gonçalves, L. G., Bonifácio, V. D. B., & Serpa, J. (2025). Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24). Biomedicine & Pharmacotherapy, 190, 118405. https://doi.org/10.1016/j.biopha.2025.118405

Editora

Elsevier

DOI

10.1016/j.biopha.2025.118405

Coleções

ESS - APCT - Artigos
ESS - CISA - Artigos

Licença CC

cclicense-by-nc

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