肺癌是全球范围内癌症相关死亡的主要原因。尽管治疗干预措施（包括外科手术、放射、化疗、靶向治疗和免疫治疗）取得了进展，但总体预后仍然不利。氧化还原平衡的不平衡和氧化还原信号的破坏是肿瘤的常见特征，在恶性进展和治疗抵抗中发挥着至关重要的作用。癌细胞的特征通常是由于遗传、代谢和微环境改变而导致活性氧 (ROS) 水平持续升高，癌细胞通过增强抗氧化能力来平衡这种情况。半胱氨酸的可用性成为化学耐药性的关键因素，影响着非小细胞肺癌 (NSCLC) 细胞的生存动态。硒-白杨素（SeChry）被公开为细胞内半胱氨酸的调节剂。本研究全面描述了 SeChry 的代谢特征，并研究了其在 NSCLC 中的细胞毒性作用。 SeChry 治疗会引起显着的代谢变化，特别是硒化合物代谢，影响糖酵解、糖异生、三羧酸 (TCA) 循环和氨基酸代谢等关键途径。此外，SeChry 还会影响乙酸盐、乳酸、葡萄糖和氨基酸等关键代谢物的水平，从而导致氧化还原稳态和细胞生物合成的破坏。 SeChry 与其他治疗方法（如糖酵解抑制和化疗）相结合，可产生更大的疗效。此外，通过利用 NSCLC 消耗乳酸的能力，研究了使用乳酸缀合的树枝状聚合物纳米粒子进行 SeChry 递送，显示出对表达单羧酸转运蛋白的癌细胞的特异性。版权所有 2024 作者。

Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non‑small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC's capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.Copyright 2024 The Author(s).