APPLIED SPECTROSCOPY
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2026
·
IF 2.2
Lijuan Huang,Meiqi Liu,Qian Zhang,Ting Yang,Yujia Wu,Dong Yan,Changqi Xu,Dingyi Liu,Jie Yu,Chenghao Chen
This study constructed a dual-substrate colorimetry based on the catalytic activity single-stranded DNA (ssDNA), i.e., 5′-GGT TGG TGT GGT TGG-3′, functionalized gold nanoparticles (AuNPs-ssDNA). By utilizing the peroxidase-mimicking activity of AuNPs and generating differential colorimetric response fingerprints through dual substrates o-phenylenediamine (OPD) and 3-amino-9-ethylcarbazole (AEC), simultaneous discrimination and quantitative detection of Fe2⁺ and Fe3⁺ were achieved. Characterization results showed that the synthesized AuNPs had an average size of about 12 nm. After functionalization, the average diameter of the formed AuNPs-ssDNA complexes increased to 13 nm, and the absorption peak position remained unchanged, indicating that ssDNA modification did not affect their dispersity and morphology. This method, combined with multivariate calibration models, can extract quantitative information from complex response patterns, with a linear detection range for both Fe2⁺ and Fe3⁺ from 0.01 to 100 μM. In practical application validation, the method was successfully used to detect iron ion concentrations in A549 cells treated with the ferroptosis inducer GPX4-IN-7. The results showed high consistency (P ≤ 0.001) with those obtained using a commercial FerroOrange detection kit, demonstrating the potential of this method for practical application in complex biological systems.
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ANALYTICAL CHEMISTRY
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2026
·Vol. 98
·期 30
·22418-22428
·
IF 7.3
Bin Yidong,Huang Lixian,Li Caiying,Zhao Jingjin,Hu Shengqiang,Zhao Shulin,Huang Yong,Zhang Liangliang
As
an emerging form of regulated cell death, ferroptosis
has been
identified as a key contributor to the pathogenesis of several diseases.
Superoxide anion (O •– 2 ), a key reactive oxygen species, is closely
associated with ferroptosis-mediated acute liver injury (ALI). The
development of in situ, real-time imaging tools capable of visualizing
O •– 2 will benefit the early diagnosis and therapeutic intervention of
ferroptosis-mediated ALI. In this work, we designed and synthesized
a photoacoustic (PA) probe, Rho-DOH, based on a rhodamine scaffold,
for the specific detection of O •– 2 . Rho-DOH exhibits a highly
sensitive, selective, and fast PA response toward O •– 2 , characterized
by a large bathochromic shift of 125 nm and an activation fold of
up to 29-fold. Cellular experiments demonstrate that Rho-DOH enables
high-contrast PA imaging of endogenous O •– 2 in cells. Moreover, Rho-DOH
was successfully applied to detect the ferroptosis-mediated ALI and
to evaluate therapeutic responses through its O •– 2 -responsive PA
imaging signal. These findings position Rho-DOH as a promising molecular
imaging tool, offering robust support for the accurate diagnosis and
treatment of ferroptosis-associated liver injury.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Ludong Tan,Xiaodong Bai,Peiyuan Yu,Tinghan Jiang,Zhe Jin
Artemisia capillaris extract alleviates acetaminophen-induced liver injury by inhibiting ferroptosis. • Capillarisin is identified as the primary bioactive constituent responsible for the hepatoprotection. • Capillarisin directly binds to and inhibits Glycogen Synthase Kinase 3β (GSK3β). • Inhibition of GSK3β by Capillarisin activates the Nrf2-mediated anti-ferroptotic pathway. • This study reveals a novel molecular mechanism for a traditional hepatoprotective herb. Background Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, characterized by oxidative stress-driven hepatocyte necrosis. Recent evidence implicates ferroptosis, an iron-dependent cell death, as a critical pathogenic event. Artemisia capillaris Thunb. (ACE) is a traditional hepatoprotective herb; however, its bioactive constituents and molecular targets regulating ferroptosis remain elusive. Purpose This study aimed to identify the bioactive compounds of ACE and elucidate the molecular mechanism underlying its protective effect against APAP-induced hepatotoxicity, with a specific focus on the ferroptosis pathway. Methods We integrated multi-omics, network pharmacology, and rigorous biophysical assays to decipher the protective mechanism. The ethanol extract of A. capillaris was chemically characterized using UPLC-LTQ-Orbitrap MS. An APAP-induced acute liver injury model in C57BL/6 mice and primary mouse hepatocytes were employed. Transcriptomics (RNA-seq) was utilized to identify key signaling pathways. The direct physical interaction between the active compound and its target was validated using Microscale Thermophoresis (MST), Cellular Thermal Shift Assay (CETSA), Drug Affinity Responsive Target Stability (DARTS), and molecular dynamics (MD) simulations. Functional validation was performed using gene overexpression and specific inhibitors. Results ACE pretreatment significantly attenuated APAP-induced liver injury, inflammation, and oxidative stress in mice. Transcriptomic profiling identified ferroptosis as a primary target pathway. Through chemical screening, we identified Capillarisin as the key bioactive coumarin responsible for this effect. Capillarisin treatment effectively suppressed lipid peroxidation, iron overload, and the expression of ferroptotic markers (COX2, ACSL4) while restoring GPX4 levels both in vivo and in vitro . Mechanistically, we demonstrated that Capillarisin acts as a direct inhibitor of Glycogen Synthase Kinase 3β (GSK3β). Capillarisin binds stably to the ATP-binding pocket of GSK3β ( K d = 0.87 µM), thereby inhibiting its kinase activity. This inhibition blocks the phosphorylation-dependent degradation of Nrf2, promoting its nuclear translocation and the subsequent transcriptional activation of anti-ferroptotic genes ( Gpx4, Slc7a11 ). Overexpression of GSK3β or pharmacological inhibition of Nrf2 abolished the protective effects of Capillarisin. Conclusion Our study reveals a novel mechanism whereby Capillarisin alleviates APAP-induced hepatotoxicity by directly targeting GSK3β to activate the Nrf2-mediated anti-ferroptosis defense. These findings provide a rigorous scientific basis for the ethnopharmacological use of Artemisia capillaris and highlight Capillarisin as a promising lead candidate for targeting GSK3β in the treatment of drug-induced liver injury. Download: Download high-res image (228KB) Download: Download full-size image
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Advanced Healthcare Materials
·
2026
·
IF 11
Zhiwen Wang,Yue Xie,Jiahui Zhang,Min Yang,Zhiyue Zou,Chun Zhang
Acute kidney injury (AKI) and chronic kidney disease (CKD), despite distinct etiologies, share a common pathological axis characterized by reactive oxygen species (ROS) burst, ferroptosis activation, and sustained inflammation. Targeting this ROS–ferroptosis–inflammation cycle represents a promising therapeutic strategy; however, current nanoplatforms are limited by insufficient responsiveness and limited capacity to regulate shared pathological mechanisms across distinct renal disease models. Here, we develop an engineered ROS-responsive nanozyme by integrating diselenide-bridged organosilica, hyaluronic acid (HA)-modified cerium oxide (CeO 2 ), and a selenium-containing diselenide framework. Under oxidative stress, MON@HA-CeO 2 undergoes ROS-triggered disassembly, coupling HA-CeO 2 -mediated ROS scavenging with selenium-related GPX4 restoration to suppress lipid peroxidation, ferroptosis, and inflammatory amplification. In both glycerol-induced AKI and unilateral ureteral obstruction (UUO)-induced renal fibrosis models, the nanozyme significantly improves renal function and attenuates tissue injury, fibrosis, and inflammation. Overall, this work demonstrates a versatile strategy for targeting a shared pathological axis and provides a promising platform for the treatment of diverse renal diseases.
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Cell Death & Disease
·
2026
·
IF 12.2
Liu Jiaxi,Miao Jiyu,Lv Yang,Fu Bingjie,Ren Xiaomin,Wang Naiqi,Xv Xuezhu,Gao Gongzhizi,Lin Zujie,Zhang Wenxiang,Zhao Bide,Shen Ying,Jia Yachun,Zhao Wanhong,Liu Rui,He Aili
Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled plasma cell proliferation and frequent therapeutic relapse. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic vulnerability in cancer. However, the mechanisms governing ferroptosis resistance in MM remain incompletely understood. Here, we identified thioredoxin (TXN), a central redox regulator, as a ferroptosis suppressor associated with poor prognosis in MM patients. Genetic knockdown or pharmacological inhibition of TXN impaired MM progression and enhanced ferroptosis-associated lipid peroxidation. Mechanistically, TXN suppression induced broad remodeling of polyunsaturated fatty acid-containing phospholipids (PUFA-PLs), particularly phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species enriched in ferroptosis-relevant PUFAs, thereby increasing ferroptosis susceptibility. Rescue experiments using a redox-deficient TXN mutant further demonstrated that the ferroptosis-suppressive function of TXN depends on its redox activity. We further identified interferon regulatory factor 1 (IRF1), which is downregulated in MM, as a transcriptional repressor of TXN. IRF1 depletion increased TXN expression and partially attenuated TXN deficiency-induced lipid peroxidation, supporting the functional relevance of the IRF1-TXN axis in ferroptosis regulation. In addition, bortezomib (BTZ)-resistant MM cells exhibited elevated TXN expression and reduced ferroptosis sensitivity. Targeting TXN restored ferroptotic vulnerability and enhanced BTZ sensitivity in MM cells. Collectively, our findings identify TXN as a critical suppressor of ferroptosis-associated phospholipid remodeling and lipid peroxidation in MM and establish the IRF1-TXN axis as a potential therapeutic target for overcoming ferroptosis resistance and improving MM treatment outcomes.
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PHARMACEUTICAL RESEARCH
·
2026
·
IF 4.1
Chen Yong,Xu Mingxin,Liu An
Purpose Triple-negative breast cancer (TNBC) lacks effective therapeutic targets. Aurisin A (AA), a natural sesterterpenoid, shows anti-TNBC potential but is limited by poor water solubility. This study aimed to develop a tumor microenvironment (TME)-responsive co-delivery hydrogel to enhance AA efficacy. Methods AA was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) to form AA@HP-β-CD, which was co-loaded with acetazolamide (ACZ) into a triple-responsive injectable hydrogel (PCG). The anti-TNBC mechanism was investigated using HCC1937 cells, focusing on ferroptosis induction. In vivo antitumor efficacy and safety were evaluated in a xenograft nude mouse model. Results AA@HP-β-CD significantly improved AA solubility and stability. Mechanistically, AA induced ferroptosis in TNBC cells by upregulating HSP90 and promoting GPX4 degradation, leading to glutathione depletion, iron accumulation, and lipid peroxidation. ACZ disrupted intracellular pH homeostasis, further sensitizing cells to AA-induced ferroptosis. The PCG hydrogel enabled sustained, TME-triggered drug release. In the xenograft model, intratumoral injection of PCG/ACZ/AA@HP-β-CD achieved a 76.3% tumor inhibition rate with no observable toxicity to major organs. Conclusions The TME-responsive PCG/ACZ/AA@HP-β-CD hydrogel integrates drug solubilization, intelligent delivery, and dual-mechanism enhancement. The combination of AA-induced ferroptosis via the HSP90/GPX4 axis and ACZ-mediated pH disruption represents a promising strategy for TNBC therapy with good biosafety.
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TOXICON
·
2026
·
IF 2.8
Jing Li,Xiaoxiao Wang,Liya Tu,Yufeng Chen
Ovarian cancer (OC) exhibits the highest mortality rate among gynecological cancers, and the development of chemotherapy resistance serves as the primary cause of patient recurrence and death. Natural products hold promise in reversing cisplatin (DDP) resistance. Trigonelline is a natural alkaloid possessing anti-tumor activity; however, it remains uncertain whether it can reverse DDP resistance in OC. In this study, DDP-resistant OC cell lines SKOV-3/DDP and A2780/DDP were successfully established. Cells were treated with non-toxic concentration of trigonelline in combination with DDP, and the molecular mechanism was investigated through the overexpression of Nrf2. Cell viability was detected to assess the sensitivity of the cells to DDP. Mitochondrial damage was evaluated by observing mitochondrial morphology, measuring mitochondrial membrane potential, ATP production, and ROS. Ferroptosis was assessed by detecting the levels of lipid peroxidation, MDA, SOD, Fe 2+ , and GSH/GSSG ratio in the cells. Additionally, the expression levels of ferroptosis-related proteins, namely Nrf2, HO-1, GPX4, and SLC7A11, were also detected. The results indicated that the utilization of low-concentration trigonelline exerted no toxic influence on OC drug-resistant cells, and instead potentiated the cytotoxicity of DDP against these cells. Furthermore, in comparison with the treatment using DDP alone, the combined treatment of trigonelline and DDP induced more severe mitochondrial damage and ferroptosis in drug-resistant cells. This led to the accumulation of ROS, notable increases in lipid peroxidation, MDA, and Fe 2+ levels within the cells, while decreasing SOD activity and the ratio of GSH/GSSG, and down-regulating the expression of Nrf2, HO-1, GPX4, and SLC7A11 proteins. Nevertheless, the overexpression of Nrf2 reversed the combined effect of trigonelline and DDP. These results indicate that trigonelline reverses DDP resistance in OC cells by promoting ferroptosis via the regulation of the Nrf2/GPX4 signaling pathway.
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Nutrients
·
2026
·Vol. 18
·期 13
·2071
·
IF 5.8
Jian-Qiang Wang,Bing-Bing Hu,Yi-Yue Wang,Ya-Wei Lu,Xiao-Jie Gong,Shan Tang,Ling-Jie Song,Yin-Shi Sun,Jing-Tian Zhang,Zi Wang,Wei Li
Objectives:Neuroinflammation is recognized as a significant characteristic of Alzheimer’s disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation.Methods:In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism.Results:Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner.Conclusions:Maltol exhibits significant protective effects against Alzheimer’s disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer’s disease neuroinflammation using traditional Chinese medicine.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Hansheng Wang,Keyi Li,Haomou Pu,Yaoyao Xiong,Dan Luo,Jinjie Song,Hongjie Jiang,Xiaoping Yu,Tao Deng
Background The molecular basis of retinal photochemical damage remains incompletely understood, limiting the development of targeted therapeutic strategies. Delphinidin, an anthocyanidin with reported protective effects, represents a promising candidate, but its direct molecular target and mechanism of action are unclear. Methods The molecular target of delphinidin was identified using Activity-Based Protein Profiling (ABPP), DARTS-MS, SPR, and CETSA. Its functional effects were investigated in 661W photoreceptor cells and in a light-induced retinal damage model in Sprague-Dawley rats. Protein carbonylation was assessed via an alkynylaniline probe, and Voltage-Dependent Anion Channel 1 (VDAC1) oligomerization was examined by chemical crosslinking. Mitochondrial function, cGAS-STING pathway activation, and ferroptosis markers were evaluated to delineate the underlying mechanism. Results VDAC1 was identified as a direct target of delphinidin. Light exposure induced VDAC1 carbonylation and oligomerization, leading to mitochondrial dysfunction characterized by cytochrome c release and mitochondrial DNA (mtDNA) leakage into the cytosol. Cytosolic mtDNA activated cGAS-STING pathway, which in turn promoted loss of the ferroptosis suppressor GPX4 and triggered ferroptosis. Delphinidin interrupted this cascade by binding to VDAC1 and inhibiting its carbonylation and oligomerization, thus limiting mtDNA leakage, attenuating cGAS-STING activation, preserving GPX4 abundance, and inhibiting ferroptosis. In vivo , delphinidin intervention conferred significant protective effects, as evidenced by preservation of retinal histoarchitecture and reduced oxidative damage and ferroptosis, Conclusion This study identifies a novel mechanistic axis in RPD linking VDAC1 dysregulation to mtDNA-driven innate immune activation and ferroptosis. It further establishes delphinidin as a direct VDAC1 targeting compound and highlights its therapeutic potential for the prevention of RPD. Download: Download high-res image (219KB) Download: Download full-size image
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2026
·
IF 9.6
Ying Zhao,Yubo Lu,Yushan Ma,Guo Ru,Weisheng Feng,Rui Niu,Yang Liu
Ferroptosis, a promising antitumour approach, is triggered by lipid peroxide (LPO) accumulation in tumour cells. However, the antioxidant defence system of tumour cells significantly restricts the efficacy of ferroptosis. Herein, we report osthole-loaded iron-based metal–organic framework nanomaterials (NH 2 -MIL-88B@Ost@PEG, NOP), a nanoenzyme, which disrupts the cellular antioxidant defence system by scavenging glutathione (GSH) and inactivating glutathione peroxidase 4 (GPX4), inducing potent immunogenic ferroptosis. In particular, NOP exhibited peroxidase-like activity, catalysing the decomposition of endogenous hydrogen peroxide (H 2 O 2 ) into bursts of highly cytotoxic hydroxyl radicals, increasing reactive oxygen species (ROS)-dependent LPO. The GSH peroxidase−like activity of NOP induced GSH conversion to oxidised glutathione in tumours, impairing the functional efficacy of GPX4. The released osthole could directly inactivate GPX4 through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway. NOP concurrently depleted GSH and inactivated GPX4, thereby potently driving LPO accumulation and inducing robust immunogenic ferroptosis. This study offers a distinct approach to achieve efficient ferroptosis. We developed an osthole-loaded Fe-MOF nanozyme that synergistically depletes GSH and inactivates GPX4 to dismantle tumour antioxidant defenses and robustly induce immunogenic ferroptosis. Download: Download high-res image (313KB) Download: Download full-size image
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RESPIRATORY RESEARCH
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2026
·
IF 5.7
Yi Yanjun,Hu Yidu,Ren Shencheng,Wu Yingting,Chen Xinran,Lu Yang,Yu Qi,Zuo Di,Bi Guoshu,Wang Qun,Zhan Cheng,Bian Yunyi
Background KRAS G12C-targeted therapies have transformed the treatment of KRAS G12C-mutant lung adenocarcinoma. However, acquired resistance to these therapies, whose underlying molecular mechanisms are not fully understood, presents a major obstacle to achieving long-term therapeutic success. The purpose of this study was to elucidate the mechanisms of acquired resistance to KRAS G12C inhibitors and identify potential regulators of resistance in lung adenocarcinoma. Methods Two lung adenocarcinoma cell lines (H23 and H2122) were exposed to escalating doses of two novel KRAS G12C inhibitors, fulzerasib and garsorasib, to generate resistant variants. Transcriptomic profiling was conducted to identify genes consistently upregulated in resistant cells. CRISPR/Cas9-mediated knockout (MXD4-KO) and siRNA-mediated knockdown of MXD4 were performed to assess its role in drug resistance. Mechanistic investigations employed inhibitors of ferroptosis, apoptosis, and necrosis, along with assays measuring lipid peroxidation and malondialdehyde levels. Further analysis included ferroptosis-related gene expression profiling, lipidomic profiling, ChIP-Seq, ChIP-qPCR, and dual-luciferase reporter assays. The findings were validated in patient-derived organoids (PDOs) and nude mouse models. Results Transcriptomic profiling identified 11 genes consistently upregulated in resistant cells, with MXD4 emerging as a key resistance regulator. CRISPR/Cas9-mediated knockout of MXD4 restored sensitivity to fulzerasib, garsorasib, sotorasib, and adagrasib, an effect fully reversed upon MXD4 re-overexpression. Similarly, siRNA-mediated knockdown of MXD4 in resistant cells restored drug sensitivity. Mechanistic studies revealed that MXD4 specifically suppresses ferroptosis, rather than apoptotic or necrotic pathways, by repressing ACSL4 expression and blocking its catalytic synthesis of phosphatidylethanolamine-polyunsaturated fatty acids (PE-PUFAs). ACSL4 knockout or overexpression abolished MXD4’s ability to promote ferroptosis suppression and resistance to KRAS G12C inhibitors. ChIP-Seq, ChIP-qPCR, and dual-luciferase reporter assays confirmed that MXD4 directly binds to and represses the ACSL4 promoter. These findings were validated in PDOs and nude mouse models, where MXD4 knockout restored therapeutic sensitivity, while ACSL4 knockout blocked MXD4’s resistance-promoting effects. Conclusions This study uncovers a novel resistance mechanism in which MXD4 transcriptionally silences ACSL4 to suppress ferroptosis, enabling cancer cells to evade KRAS G12C inhibitors. Targeting the MXD4-ACSL4 axis represents a promising strategy to overcome therapeutic resistance in KRAS G12C-mutant lung cancer, potentially improving long-term treatment outcomes.
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Acta Biomaterialia
·
2026
·
IF 10.4
Zhong Shao,Hao Guo,Ke Li,Xiang Li,Zhiyuan Tan,Yangyang Cheng,Shiyong Zhang
Intervening in the aberrant redox homeostasis of tumors, particularly toward reactive oxygen species (ROS) overload, holds considerable promise for cancer therapy, yet, is severely constrained by the robust compensatory antioxidant defense system (ADS) and the unavoidable disruption of redox homeostasis in normal tissues. Here, we present a catalytic redox-cycling nanoreactor, TEMPO radical-modified cross-linked lipoic acid nanoparticles (T@cLAN), designed to achieve robust oxidative stress amplification for cancer therapy. Lipoic acid (LA) characterized by a cyclic disulfide backbone enables intermolecular thiol–disulfide exchange to from GSH-responsive crosslinked networks, while enabling reversible interconversion with dihydrolipoic acid (DHLA), which can further participate in redox modulation. Mechanistically, T@cLAN depletes intracellular glutathione (GSH) and undergoes depolymerization to generate dihydrolipoic acid (DHLA), which actively participates in redox processes to enhance ROS production. TEMPO, functions as a catalyst rather than a stoichiometric scavenger, directly accelerating the endogenous LA/DHLA redox cycle, thereby further amplifying DHLA generation and sustaining both GSH depletion and ROS amplification. As validated by both in vitro and in vivo results, T@cLAN dismantles the major ADS barrier limiting tumor oxidative stress, achieving an overall 85% GSH depletion and elevating ROS levels by 37-fold compared to untreated tumor cells. Concurrently, it induces both apoptosis and ferroptosis, attaining a tumor inhibition rate of 80% while causing minimal impact on normal cells and tissues, underscoring its substantial potential for cancer therapy. Statement of significance We engineer a nanoreactor (T@cLAN) as an innovative modality to address a central limitation of oxidative stress–mediated anticancer therapy, that is, the therapeutic attenuation imposed by the highly developed antioxidant defense machinery of tumor cells. T@cLAN is activated by intracellular glutathione, a key redox buffer, to engage two interlinked redox catalytic cycles, enabling sustained glutathione depletion and the amplified accumulation of cytotoxic reactive oxygen species. Through this cooperative redox reprogramming, T@cLAN promotes tumor cell apoptosis and ferroptosis, leading to pronounced anticancer activity. Notably, T@cLAN is activated within the tumor microenvironment while remaining largely quiescent in normal cells, reflecting an active and highly selective intervention mechanism that offers new directions for oxidative stress driven therapeutic innovation. Download: Download high-res image (228KB) Download: Download full-size image
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