Mn(II)-Aloe-Emodin Nanoscale Coordination Polymer Enhances Ferroptosis by Synergistically Enhancing Reactive Oxygen Species Generation via the Nrf2-GPX4 Axis.

Ferroptosis induction is particularly promising for cancer therapy when the apoptosis pathway is compromised. Current strategies in nanomedicine for inducing ferroptosis primarily focus on promoting the accumulation of reactive oxygen species (ROS). However, the presence of intracellular antioxidants, such as nuclear factor erythroid 2-related factor 2 (Nrf2), can limit the effectiveness of such therapy by activating detoxification systems and eliminating ROS. To overcome this challenge, a simple one-step strategy for the construction of Mn2+-aloe-emodin (AE) nanoscale coordination polymers (MAP NPs) with ultrahigh loading capacity, followed by the modification of polyvinyl pyrrolidone (PVP), was developed. In the tumour microenvironment (TME), these NPs degraded and released AE and Mn(II), facilitating the generation of ROS and Mn(IV) through a Fenton-like reaction between H2O2 and Mn(II). Mn(IV) subsequently interacted with glutathione (GSH) to induce a cyclic catalytic effect, and the depletion of GSH diminished the activation of glutathione-dependent peroxidase 4 (GPX4). Furthermore, AE inhibited the activity of Nrf2 and depleted GSH, thereby synergistically enhancing antitumour efficacy. Our study demonstrated that MAP NPs effectively generate a robust ROS storm within tumour cells, suggesting that high-performance ferroptosis therapy is effective. Additionally, the inclusion of Mn(II) in the MAP NPs enabled real-time monitoring of therapeutic efficacy via magnetic resonance T1-weighted contrast imaging. This article is protected by copyright. All rights reserved.

Effects and mechanisms of N6-methyladenosine RNA methylation in environmental pollutant-induced carcinogenesis.

Environmental pollution, including air pollution, plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases and is a critical risk factor for chronic health conditions, including cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m6A) as a crucial regulatory mechanism in pathological processes and cancer progression. Governed by m6A writers, erasers, and readers, m6A orchestrates alterations in target gene expression, consequently playing a vital role in a spectrum of RNA processes, covering mRNA processing, translation, degradation, splicing, nuclear export, and folding. Thus, there is a growing need to pinpoint specific m6A-regulated targets in environmental pollutant-induced carcinogenesis, an emerging area of research in cancer prevention. This review consolidates the understanding of m6A modification in environmental pollutant-induced tumorigenesis, explicitly examining its implications in lung, skin, and bladder cancer. We also investigate the biological mechanisms that underlie carcinogenesis originating from pollution. Specific m6A methylation pathways, such as the HIF1A/METTL3/IGF2BP3/BIRC5 network, METTL3/YTHDF1-mediated m6A modification of IL 24, METTL3/YTHDF2 dynamically catalyzed m6A modification of AKT1, METTL3-mediated m6A-modified oxidative stress, METTL16-mediated m6A modification, site-specific ATG13 methylation-mediated autophagy, and the role of m6A in up-regulating ribosome biogenesis, all come into play in this intricate process. Furthermore, we discuss the direction regarding the interplay between pollutants and RNA metabolism, particularly in immune response, providing new information on RNA modifications for future exploration.

Local therapy combined with anti-PD-1 immunotherapy for advanced lung adenocarcinoma: A case report.

ABSTRACT: Lung adenocarcinoma (LUAD) encompasses all lung epithelial cancers except small-cell lung cancer. Although programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab, and other Food and Drug Administration-approved immune checkpoint inhibitors, offer new hope for LUAD treatment, LUAD's overall efficacy remains limited. Thus, the combination of immunotherapy with other therapeutic approaches has gained widespread attention. Local therapy is an optimal method for treating many advanced unresectable lung cancers. Herein, we present a case of a patient with multiple metastases from LUAD, who attained complete response for more than 3 years until present through local therapy combined with a PD-1 inhibitor.

Oxophilic Ce single atoms-triggered active sites reverse for superior alkaline hydrogen evolution.

The state-of-the-art alkaline hydrogen evolution catalyst of united ruthenium single atoms and small ruthenium nanoparticles has sparked considerable research interest. However, it remains a serious problem that hydrogen evolution primarily proceeds on the less active ruthenium single atoms instead of the more efficient small ruthenium nanoparticles in the catalyst, hence largely falling short of its full activity potential. Here, we report that by combining highly oxophilic cerium single atoms and fully-exposed ruthenium nanoclusters on a nitrogen functionalized carbon support, the alkaline hydrogen evolution centers are facilely reversed to the more active ruthenium nanoclusters driven by the strong oxophilicity of cerium, which significantly improves the hydrogen evolution activity of the catalyst with its mass activity up to -10.1 A mg-1 at -0.05 V. This finding is expected to shed new light on developing more efficient alkaline hydrogen evolution catalyst by rational regulation of the active centers for hydrogen evolution.

Modulating the Distribution of Formamidinium Iodide by Ultrahigh Humidity Treatment Strategy for High-Quality Sequential Vapor Deposited Perovskite.

The quality of two-step processed perovskites is significantly influenced by the distribution of organic amine salts. Especially, modulating the distribution of organic amine salts remains a grand challenge for sequential vapor-deposited perovskites due to the blocking effect of bottom compact PbI2. Herein, an ultrahigh humidity treatment strategy is developed to facilitate the diffusion of formamidinium iodide (FAI) from the top surface to the buried bottom interface on the sequential vapor-deposited bilayer structure. Both experimental and theoretical investigations elucidate the mechanism that moisture helps to i) create FAI diffusion channels by inducing a phase transition from α- to δ-phase in the perovskite, and ii) enhance the diffusivity of FAI by forming hydrogen bonds. This ultrahigh humidity treatment strategy enables the formation of a desired homogeneous and high-quality α-phase after annealing. As a result, a champion efficiency of 22.0% is achieved and 97.5% of its initial performance is maintained after aging for 1050 h under ambient air with a relative humidity of up to 80%. This FAI diffusion strategy provides new insights into the reproducible, scalable, and high-performance sequential vapor-deposited perovskite solar cells.

A nanoscale MOF-based heterogeneous catalytic system for the polymerization of N-carboxyanhydrides enables direct routes toward both polypeptides and related hybrid materials.

Synthetic polypeptides have emerged as versatile tools in both materials science and biomedical engineering due to their tunable properties and biodegradability. While the advancements of N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques have aimed to expedite polymerization and reduce environment sensitivity, the broader implications of such methods remain underexplored, and the integration of ROP products with other materials remains a challenge. Here, we show an approach inspired by the success of many heterogeneous catalysts, using nanoscale metal-organic frameworks (MOFs) as co-catalysts for NCA-ROP accelerated also by peptide helices in proximity. This heterogeneous approach offers multiple advantages, including fast kinetics, low environment sensitivity, catalyst recyclability, and seamless integration with hybrid materials preparation. The catalytic system not only streamlines the preparation of polypeptides and polypeptide-coated MOF complexes (MOF@polypeptide hybrids) but also preserves and enhances their homogeneity, processibility, and overall functionalities inherited from the constituting MOFs and polypeptides.

Facet-controlled assembly for organizing metal-organic framework particles into extended structures.

Metal-organic frameworks (MOFs) are crystalline porous materials characterized by their high porosity and chemical tailorability. To realize the full potential of synthesized MOFs, it is important to transform them from crystalline solid powders into materials with integrated morphologies and properties. One promising approach is facet-controlled assembly, which involves arranging individual crystalline MOF particles into ordered macroscale structures by carefully controlling the interactions between particles. The resulting assembled MOF structures maintain the characteristics of individual particles while also exhibiting improved properties overall. In this article, we emphasize the essential concepts of MOF assembly, highlighting the impact of building blocks, surface interactions, and Gibbs free energy on the assembly process. We systematically examine three methods of guiding facet-controlled MOF assembly, including spontaneous assembly, assembly guided by external forces, and assembly through surface modifications. Lastly, we offer outlooks on future advancements in the fabrication of MOF-based material and potential application exploration.

Sorting of Cluster-Confined Metallic Single-Walled Carbon Nanotubes for Fabricating Atomically Vacant Uranium Oxide.

Single-walled carbon nanotube (SWCNT) heterostructures have shown great potential in catalysis, magnetism, and nanofluidics, in which host SWCNTs with certain conductivity (metallic or semiconducting) are highly required. Herein, inspired by the large molecular weight and redox properties of polyoxometalate (POM) clusters, we reported the selective separation of POM encapsulated metallic SWCNTs (POM@m-SWCNTs) with a uniform diameter through density gradient ultracentrifugation (DGU). The confined POMs increased the SWCNT density and amplified the nanotubes' density difference, thus greatly lowering the centrifugal force (70,000g) of DGU. With this strategy, a series of POM@m-SWCNTs of ∼1.2 nm with high purity were sorted. The mechanism supported by theoretical and experimental evidence showed that the separation of m-SWCNTs depended on not only nanotube/cluster size but also the conductivity of SWCNTs. The smallest 1.2 nm m-SWCNT that can exactly accommodate a 0.9 nm-{Mo6} cluster exhibited the maximum electron transfer to inner clusters; thus, intertube π-π stacking of such m-SWCNTs was greatly loosened, leading to the preferential dispersion into individual ones and partitioning in the uppermost layer after DGU. As a proof-of-concept application, this sorting strategy was extended to separate heavy-element 238U-encapsulated m-SWCNTs. The phase-pure, tiny (1-2.5 nm) U4O9 crystals with atomic vacancy clusters were fabricated on m-SWCNTs through growth kinetic control. This work may provide a general way to construct desired actinide materials on specific SWCNTs.

Magnetic Topological Insulator MnBi2Te4 Nanosheets for Femtosecond Pulse Generation.

The van der Waals layered material MnBi2Te4, as a magnetic topological insulator, has attracted tremendous interest for novel physics research in the fields of condensed matter physics and materials science. However, the nonlinear optical properties of MnBi2Te4 and its applications in ultrafast optics have rarely been explored. In this study, high-quality MnBi2Te4 nanosheets have been successfully synthesized by the self-flux method. The morphology, chemical composition, magnetic properties, and nonlinear optical characteristics were systematically investigated. The magnetic transition of MnBi2Te4 was confirmed by a low-temperature spatially resolved spectroscopic technique. The saturable absorption property of MnBi2Te4 was measured by a balanced twin-detector system with a modulation depth of 4.5% and a saturation optical intensity of 2.35 GW/cm2. Furthermore, by inserting the MnBi2Te4-based saturable absorber, a soliton mode-locking laser operating at 1558.8 nm was obtained with a pulse duration of 331 fs. This research will pave the way for applications of the magnetic TI MnBi2Te4 in nonlinear optics and photonics.

A cage-on-MOF strategy to coordinatively functionalize mesoporous MOFs for manipulating selectivity in adsorption and catalysis.

Functionalizing porous materials with capping agents generates hybrid materials with enhanced properties, while the challenge is how to improve the selectivity and maintain the porosity of the parent framework. Herein, we developed a "Cage-on-MOF" strategy to tune the recognition and catalytic properties of MOFs without impairing their porosity. Two types of porous coordination cages (PCCs) of opposite charges containing secondary binding groups were developed to coordinatively functionalize two distinct porous MOFs, namely MOF@PCC nanocomposites. We demonstrated that the surface-capped PCCs can act as "modulators" to effectively tune the surface charge, stability, and adsorption behavior of different host MOF particles. More importantly, the MOF@PCCs can serve as selective heterogeneous catalysts for condensation reactions to achieve reversed product selectivity and excellent recyclability. This work sets the foundation for using molecular cages as porous surface-capping agents to functionalize and manipulate another porous material, without affecting the intrinsic properties of the parent framework.

A Dihydroartemisinin-Loaded Nanoreactor Motivates Anti-Cancer Immunotherapy by Synergy-Induced Ferroptosis to Activate Cgas/STING for Reprogramming of Macrophage.

Infiltration of tumor-associated macrophages (TAM) characterized by an M2 phenotype is an overriding feature in malignant tumors. Reprogramming TAM is the most cutting-edge strategy for cancer therapy. In the present study, an iron-based metal-organic framework (MOF) nanoreactor loaded with dihydroartemisinin (DHA) is developed, which provides high uptake by TAM and retains their viability, thus effectively addressing the inefficiency of the DHA at low concentrations. Impressively, DHA@MIL-101 can selectively accumulate in tumor tissues and remodel TAM to the M1 phenotype. The results of RNA sequencing further suggest that this nanoreactor may regulate ferroptosis, a DNA damage signaling pathway in TAM. Indeed, the outcomes confirm that DHA@MIL-101 triggers ferroptosis in TAM. In addition, the findings reveal that DNA damage induced by DHA nanoreactors activates the intracellular cGAS sensor, resulting in the binding of STING to IRF3 and thereby up-regulating the immunogenicity. In contrast, blocking ferroptosis impairs DHA@MIL-101-induced activation of STING signaling and phenotypic remodeling. Finally, it is shown that DHA nanoreactors deploy anti-tumor immunotherapy through ferroptosis-mediated TAM reprogramming. Taken together, immune efficacy is achieved through TAM's remodeling by delivering DHA and iron ions into TAM using nanoreactors, providing a novel approach for combining phytopharmaceuticals with nanocarriers to regulate the immune microenvironment.

Metal-organic framework-encapsulated dihydroartemisinin nanoparticles induces apoptotic cell death in ovarian cancer by blocking ROMO1-mediated ROS production.

Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

Metal-Organic Framework Nanoparticles with Universal Dispersibility through Crown Ether Surface Coordination for Phase-Transfer Catalysis and Separation Membranes.

Dispersing metal-organic framework (MOF) solids in stable colloids is crucial for their availability and processibility. Herein, we report a crown ether surface coordination approach for functionalizing the surface-exposed metal sites of MOF particles with amphiphilic carboxylated crown ether (CEC ). The surface-bound crown ethers significantly improve MOF solvation without compromising the accessible voids. We demonstrate that CEC -coated MOFs exhibit exceptional colloidal dispersibility and stability in 11 distinct solvents and six polymer matrices with a wide range of polarities. The MOF-CEC can be instantaneously suspended in immiscible two-phase solvents as an effective phase-transfer catalyst and can form various uniform membranes with enhanced adsorption and separation performance, which highlights the effectiveness of crown ether coating.

Ternary GePdS3: 1D van der Waals Nanowires for Integration of High-Performance Flexible Photodetectors.

One-dimensional (1D) van der Waals (vdW) materials are anticipated to leverage for high-performance, giant polarized, and hybrid-dimension photodetection owing to their dangling-bond free surface, intrinsic crystal structure, and weak vdW interaction. However, only a few related explorations have been conducted, especially in the field of flexible and integrated applications. Here, high-quality 1D vdW GePdS3 nanowires were synthesized and proven to be an n-type semiconductor. The Raman vibration and band gap (1.37-1.68 eV, varying from bulk to single chain) of GePdS3 were systemically studied by experimental and theoretical methods. The photodetector based on a single GePdS3 nanowire possesses fast photoresponse at a broadband spectrum of 254-1550 nm. The highest responsivity and detectivity reach up to ∼219 A/W and ∼2.7 × 1010 Jones (under 254 nm light illumination), respectively. Furthermore, an image sensor with 6 × 6 pixels based on GePdS3 nanowires is integrated on a flexible polyethylene terephthalate (PET) substrate and exhibits sensitive and homogeneous detection at 808 nm light. These results indicate that the ternary noble metal chalcogenides show great potential in flexible and broadband optoelectronics applications.

Modulation of internal solitary waves by the Kuroshio in the northern South China Sea.

Internal solitary waves (ISWs) in the South China Sea (SCS) are considerably modulated by the background currents. In this study, a three-dimensional high-resolution non-hydrostatic model is configured to investigate how the Kuroshio influences the generation and evolution of ISWs in the northern SCS. Three runs are conducted, including one control experiment without the Kuroshio and two sensitivity experiments with the Kuroshio in different paths. In the Luzon Strait (LS), the Kuroshio reduces the westward baroclinic energy flux radiated into the SCS, resulting in weakened ISWs. In the SCS basin, the background currents further refract the ISWs. With the leaping Kuroshio, the A-waves have longer crest lines but lower amplitudes compared with those in the control run. In contrast, the B-waves are less affected by the leaping Kuroshio. In the presence of looping Kuroshio, the wave refraction caused by the intrusion currents in the SCS basin results in the weakest amplitudes and energy but the widest crest lines of ISWs. Moreover, the energy of the A-waves exhibits double-peak structure along the crest lines. The crest lines of the B-waves extend to 19.5° N, which are more south than those in summer. These results highlight the importance of the Kuroshio on the 3D features of ISWs in the SCS.

A graph neural network-based bearing fault detection method.

Bearings are very important components in mechanical equipment, and detecting bearing failures helps ensure healthy operation of mechanical equipment and can prevent catastrophic accidents. Most of the well-established detection methods do not take into account the correlation between signals and are difficult to accurately identify those fault samples that have a low degree of failure. To address this problem, we propose a graph neural network-based bearing fault detection (GNNBFD) method. The method first constructs a graph using the similarity between samples; secondly the constructed graph is fed into a graph neural network (GNN) for feature mapping, and the samples outputted by the GNN network fuse the feature information of their neighbors, which is beneficial to the downstream detection task; then the samples mapped by the GNN network are fed into base detector for fault detection; finally, the results determined by the integrated base detector algorithm are determined, and the top n samples with the highest outlier scores are the faulty samples. The experimental results with five state-of-the-art algorithms on publicly available datasets show that the GNNBFD algorithm improves the AUC by 6.4% compared to the next best algorithm, proving that the GNNBFD algorithm is effective and feasible.

Dihydroartemisinin elicits immunogenic death through ferroptosis-triggered ER stress and DNA damage for lung cancer immunotherapy.

BACKGROUND: The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism. METHODS: The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model. The apoptosis, ferroptosis assay, western blotting, immunofluorescent staining, qPCR, comet assay, flow cytometry, confocal microscopy, transmission electron microscopy and immunohistochemistry were conducted to analyze the functions and the underlying mechanism. RESULTS: An increased apoptosis rate and immunogenicity were detected in DHA-treated LLC and tumor grafts. Further findings showed DHA caused lipid peroxide (LPO) accumulation, thereby initiating ferroptosis. DHA stimulated cellular endoplasmic reticulum (ER) stress and DNA damage simultaneously. However, the ER stress and DNA damage induced by DHA could be abolished by ferroptosis inhibitors, whose immunogenicity enhancement was synchronously attenuated. In contrast, the addition of exogenous iron ions further improved the immunogenicity induced by DHA accompanied by enhanced ER stress and DNA damage. The enhanced immunogenicity could be abated by ER stress and DNA damage inhibitors as well. Finally, DHA activated immunocytes and exhibited excellent anti-cancer efficacy in LLC-bearing mice. CONCLUSIONS: In summary, the current study demonstrates that DHA triggers ferroptosis, facilitating the ICD of lung cancer thereupon. This work reveals for the first time the effect and underlying mechanism by which DHA induces ICD of cancer cells, providing novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.

Chlorin e6-induced photodynamic effect facilitates immunogenic cell death of lung cancer as a result of oxidative endoplasmic reticulum stress and DNA damage.

Suppression of the immune microenvironment is an important endogenous contributor to treatment failure in lung cancer. Photodynamic therapy (PDT) is widely used in the treatment of malignant tumors owing to its photo-selectivity and minimal side effects. Some studies have shown the ability of photodynamic action not only to cause photo-cytotoxicity to tumor cells but also to induce immunogenic cell death (ICD). However, the mechanism by which PDT enhances tumor immunogenicity is poorly understood. The present study aimed to explore the immunogenicity effect of PDT on lung cancer and to reveal the underlying mechanism. First, we searched for effective conditions for PDT-induced apoptosis in lung cancer cells. Just as expected, chlorin e6 (Ce6) PDT could enhance the immunogenicity of lung cancer cells alongside the induction of apoptosis, characterized by up-regulation of CRT, HSP90, HMGB1 and MHC-I. Further results showed the generation of ROS by Ce6 PDT under the above conditions, which is an oxidative damaging agent. Simultaneously, PDT induced endoplasmic reticulum (ER) stress in cells, as evidenced by enhanced Tht staining and up-regulated CHOP and GRP78 expression. Moreover, PDT led to DNA damage response (DDR) as well. However, the redox inhibitor NAC abolished the ER stress and DDR caused by PDT. More importantly, NAC also attenuated PDT-induced improvement of immunogenicity in lung cancer. On this basis, the PDT-induced CRT up-regulation was found to be attenuated in response to inhibition of ER stress. In addition, PDT-induced increase in HMGB1 and HSP90 release was blocked by inhibition of DDR. In summary, Ce6 PDT could produce ROS under certain conditions, which leads to ER stress that promotes CRT translocation to the cell membrane, and the resulting DNA damage causes the expression and release of nuclear HMGB1 and HSP90, thereby enhancing the immunogenicity of lung cancer. This current study elucidates the mechanism of PDT in ameliorating the immunogenicity of lung cancer, providing a rationale for PDT in regulating the immune microenvironment for the treatment of malignant tumors.

Dihydroartemisinin remodels macrophage into an M1 phenotype via ferroptosis-mediated DNA damage.

Lung cancer recruits tumor-associated macrophages (TAMs) massively, whose predominantly pro-tumor M2 phenotype leads to immunosuppression. Dihydroartemisinin (DHA) has been proven to remodel TAM into an anti-tumor M1 phenotype at certain concentrations in the present study, which was hypothesized to facilitate anti-lung cancer immunotherapy. However, how DHA remodels the TAM phenotype has not yet been uncovered. Our previous work revealed that DHA could trigger ferroptosis in lung cancer cells, which may also be observed in TAM thereupon. Sequentially, in the current study, DHA was found to remodel TAM into the M1 phenotype in vitro and in vivo. Simultaneously, DHA was observed to trigger ferroptosis in TAM and cause the DNA damage response and NF-κB activation. Conversely, the DHA-induced DNA damage response and NF-κB activation in TAM were attenuated after the inhibition of ferroptosis in TAM using an inhibitor of ferroptosis. Importantly, a ferroptosis inhibitor could also abolish the DHA-induced phenotypic remodeling of TAM toward the M1 phenotype. In a nutshell, this work demonstrates that DHA-triggered ferroptosis of TAM results in DNA damage, which could activate downstream NF-κB to remodel TAM into an M1 phenotype, providing a novel strategy for anti-lung cancer immunotherapy. This study offers a novel strategy and theoretical basis for the use of traditional Chinese medicine monomers to regulate the anti-tumor immune response, as well as a new therapeutic target for TAM phenotype remodeling.

A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin.

BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.