Electrocatalytic functional group conversion-based carbon resource upgrading.

The conversions of carbon resources, such as alcohols, aldehydes/ketones, and ethers, have been being one of the hottest topics most recently for the goal of carbon neutralization. The emerging electrocatalytic upgrading has been regarded as a promising strategy aiming to convert carbon resources into value-added chemicals. Although exciting progress has been made and reviewed recently in this area by mostly focusing on the explorations of valuable anodic oxidation or cathodic reduction reactions individually, however, the reaction rules of these reactions are still missing, and how to purposely find or rationally design novel but efficient reactions in batches is still challenging. The properties and transformations of key functional groups in substrate molecules play critically important roles in carbon resources conversion reactions, which have been paid more attention to and may offer hidden keys to achieve the above goal. In this review, the properties of functional groups are addressed and discussed in detail, and the reported electrocatalytic upgrading reactions are summarized in four categories based on the types of functional groups of carbon resources. Possible reaction pathways closely related to functional groups will be summarized from the aspects of activation, cleavage and formation of chemical bonds. The current challenges and future opportunities of electrocatalytic upgrading of carbon resources are discussed at the end of this review.

Electrocatalytic ORR-coupled ammoximation for efficient oxime synthesis.

State-of-the-art technology for cyclohexanone oxime production typically demands elevated temperature and pressure, along with the utilization of expensive hydroxylamine sulfate or oxidants. Here, we propose an electrochemistry-assisted cascade strategy for the efficient cyclohexanone ammoximation under ambient conditions by using in situ cathode-generated green oxidants of reactive oxygen species (ROS) such as OOH* and H2O2. This electrochemical reaction can take place at the cathode, achieving over 95% yield, 99% selectivity of cyclohexanone oxime, and an electron-to-oxime (ETO) efficiency of 96%. Mechanistic analysis reveals that, in addition to the direct ammoximation by in situ-generated OOH* by electrocatalytic ORR, Ti-MOR also play a major role in capturing OOH* directly and converting the in situ-generated H2O2 to OOH*, thus accelerating the ORR-coupled cascade production of cyclohexanone oxime. This work paves a mild, economical, and sustainable energy-efficient electrocatalytic route for the oxime production using oxygen, ammonium bicarbonate, and cyclohexanone.

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

Pd/NiMoO4/NF electrocatalysts for the efficient and ultra-stable synthesis and electrolyte-assisted extraction of glycolate.

Electrocatalytic conversion of organic small molecules is a promising technique for value-added chemical productions but suffers from high precious metal consumption, poor stability of electrocatalysts and tedious product separation. Here, a Pd/NiMoO4/NF electrocatalyst with much lowered Pd loading amount (3.5 wt.%) has been developed for efficient, economic, and ultra-stable glycolate synthesis, which shows high Faradaic efficiency (98.9%), yield (98.8%), and ultrahigh stability (1500 h) towards electrocatalytic ethylene glycol oxidation. Moreover, the obtained glycolic acid has been converted to value-added sodium glycolate by in-situ acid-base reaction in the NaOH electrolyte, which is atomic efficient and needs no additional acid addition for product separation. Moreover, the weak adsorption of sodium glycolate on the catalyst surface plays a significant role in avoiding excessive oxidation and achieving high selectivity. This work may provide instructions for the electrocatalyst design as well as product separation for the electrocatalytic conversions of alcohols.

An explainable long short-term memory network for surgical site infection identification.

BACKGROUND: Currently, surgical site infection surveillance relies on labor-intensive manual chart review. Recently suggested solutions involve machine learning to identify surgical site infections directly from the medical record. Deep learning is a form of machine learning that has historically performed better than traditional methods while being harder to interpret. We propose a deep learning model, a long short-term memory network, for the identification of surgical site infection from the medical record with an attention layer for explainability. METHODS: We retrieved structured data and clinical notes from the University of Utah Health System's electronic health care record for operative events randomly selected for manual chart review from January 2016 to June 2021. Surgical site infection occurring within 30 days of surgery was determined according to the National Surgical Quality Improvement Program definition. We trained the long short-term memory model along with traditional machine learning models for comparison. We calculated several performance metrics from a holdout test set and performed additional analyses to understand the performance of the long short-term memory, including an explainability analysis. RESULTS: Surgical site infection was present in 4.7% of the total 9,185 operative events. The area under the receiver operating characteristic curve and sensitivity of the long short-term memory was higher (area under the receiver operating characteristic curve: 0.954, sensitivity: 0.920) compared to the top traditional model (area under the receiver operating characteristic curve: 0.937, sensitivity: 0.736). The top 5 features of the long short-term memory included 2 procedure codes and 3 laboratory values. CONCLUSION: Surgical site infection surveillance is vital for the reduction of surgical site infection rates. Our explainable long short-term memory achieved a comparable area under the receiver operating characteristic curve and greater sensitivity when compared to traditional machine learning methods. With explainable deep learning, automated surgical site infection surveillance could replace burdensome manual chart review processes.

Mild magnetic hyperthermia-activated immuno-responses for primary bladder cancer therapy.

Surgical intervention followed by chemotherapy is the principal treatment strategy for bladder cancer, which is hindered by significant surgical risks, toxicity from chemotherapy, and high rates of recurrence after surgery. In this context, a novel approach using mild magnetic hyperthermia therapy (MHT) for bladder cancer treatment through the intra-bladder delivery of magnetic nanoparticles is presented for the first time. This method overcomes the limitations of low magnetic thermal efficiency, inadequate tumor targeting, and reduced therapeutic effectiveness associated with the traditional intravenous administration of magnetic nanoparticles. Core-shell Zn-CoFe2O4@Zn-MnFe2O4 (MNP) nanoparticles were developed and further modified with hyaluronic acid (HA) to enhance their targeting ability toward tumor cells. The application of controlled mild MHT using MNP-HA at temperatures of 43-44 °C successfully suppressed the proliferation of bladder tumor cells and tumor growth, while also decreasing the expression levels of heat shock protein 70 (HSP70). Crucially, this therapeutic approach also activated the body's innate immune response involving macrophages, as well as the adaptive immune responses of dendritic cells (DCs) and T cells, thereby reversing the immunosuppressive environment of the bladder tumor and effectively reducing tumor recurrence. This study uncovers the potential immune-activating mechanism of mild MHT in the treatment of bladder cancer and confirms the effectiveness and safety of this strategy, indicating its promising potential for the clinical management of bladder cancer with a high tendency for relapse.

NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference.

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy-D-glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000-1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system.

In Situ Piezoelectric-Catalytic Anti-Inflammation Promotes the Rehabilitation of Acute Spinal Cord Injury in Synergy.

Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.

Construction of Ru Single-Atoms on Ceria to Reform the Products of CO2 Photoreduction.

Highly selective production of CH4 from photocatalytic CO2 reduction is still a great challenge which involves the kinetically unfavorable transfers of 8 protons and 8 electrons. Herein, CeO2 photocatalysts incorporated with isolated Ru single-atoms have been fabricated, which demonstrate dramatically elevated selectivity of CH4 from CO2 reduction. The introduced Ru single-atoms promote carrier separation and accelerate electron transfer, which efficiently enhances the photocatalytic activity. Density functional theory (DFT) calculations and in situ FT-IR analysis manifest that the Ru single-atom active sites play an indispensable role in strengthening the adsorption of *CO intermediate on the catalyst surface and promoting H2O oxidation to generate abundant protons, thus favoring *CO protonation into *CHxO (x = 1, 2, 3) species and final deoxygenation into CH4. This work provides an effective strategy by constructing single-atom active sites to modulate and stabilize the key intermediates of CO2 photoreduction to improve the selectivity of the target products.

Dual-Site Biomimetic Cu/Zn-MOF for Atopic Dermatitis Catalytic Therapy via Suppressing FcγR-Mediated Phagocytosis.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that carries a significant global economic burden. Elevated levels of reactive oxygen species (ROS) have been recognized as contributing to AD exacerbation, making them a potential therapeutic target for AD treatment. Here, we introduce a dual-site biomimetic copper/zinc metal-organic framework (Cu/Zn-MOF) featuring four types of enzyme-like activities for AD treatment via suppressing the Fcγ receptor (FcγR)-mediated phagocytosis signal by mimicking the bimetallic sites of natural copper-zinc superoxide dismutase (CuZn-SOD). Interestingly, the neighboring Cu and Zn sites in both Cu/Zn-MOF and CuZn-SOD are at similar distances of ∼5.98 and ∼6.3 Šfrom each other, respectively, and additionally, both Cu and Zn sites are coordinated to nitrogen atoms in both structures, and the coordinating ligands to Cu and Zn are both imidazole rings. Cu/Zn-MOF exhibits remarkable SOD-like activity as well as its glutathione peroxidase (GPx)-, thiol peroxidase (TPx)-, and ascorbate peroxidase (APx)-like activities to continuously consume ROS and mitigate oxidative stress in keratinocytes. Animal experiments show that Cu/Zn-MOF outperforms halcinonide solution (a potent steroid medication) in terms of preventing mechanical injuries, reducing cutaneous water loss, and inhibiting inflammatory responses while presenting favorable biosafety. Mechanistically, Cu/Zn-MOF functions through an FcγR-mediated phagocytosis signal pathway, decreasing the continuous accumulation of ROS in AD and ultimately suppressing disease progression. These findings will provide an effective paradigm for AD therapy and contribute to the development of two-site bionics (TSB).

H* Species Regulation by Mn-Co(OH)2 for Efficient Nitrate Electro-reduction in Neutral Solution.

During the electrocatalytic NO3 - reduction reaction (NO3 - RR) under neutral condition, the activation of H2 O to generate H* and the inhibition of inter-H* species binding, are critically important but remain challenging for suppressing the non-desirable hydrogen evolution reaction (HER). Here, a Mn-doped Co(OH)2 (named as Mn-Co(OH)2 ) has been synthesized by in situ reconstruction in the electrolyte, which is able to dissociate H2 O molecules but inhibits the binding of H* species between each other owing to the increased interatomic spacing by the Mn-doping. The Mn-Co(OH)2 electrocatalyst offers a faradaic efficiency (FE) of as high as 98.9±1.7% at -0.6 V vs. the reversible hydrogen electrode (RHE) and an energy efficiency (EE) of 49.90±1.03% for NH3 production by NO3 - RR, which are among the highest of the recently reported state-of-the-art catalysts in neutral electrolyte. Moreover, negligible degradation at -200 mA cm-2 has been found for at least 500 h, which is the longest catalytic durations ever reported. This work paves a novel approach for the design and synthesis of efficient NO3 - RR electrocatalysts.

Nanocatalytic Anti-Tumor Immune Regulation.

Immunotherapy has brought a new dawn for human being to defeat cancer. Although existing immunotherapy regimens (CAR-T, etc.) have made breakthroughs in the treatments of hematological cancer and few solid tumors such as melanoma, the therapeutic efficacy on most solid tumors is still far from being satisfactory. In recent years, the researches on tumor immunotherapy based on nanocatalytic materials are under rapid development, and significant progresses have been made. Nanocatalytic medicine has been demonstrated to be capable of overcoming the limitations of current clinicnal treatments by using toxic chemodrugs, and exhibits highly attractive advantages over traditional therapies, such as the enhanced and sustained therapeutic efficacy based on the durable catalytic activity, remarkably reduced harmful side-effects without using traditional toxic chemodrugs, and so on. Most recently, nanocatalytic medicine has been introduced in the immune-regulation for disease treatments, especially, in the immunoactivation for tumor therapies. This article presents the most recent progresses in immune-response activations by nanocatalytic medicine-initiated chemical reactions for tumor immunotherapy, and elucidates the mechanism of nanocatalytic medicines in regulating anti-tumor immunity. By reviewing the current research progress in the emerging field, this review will further highlight the great potential and broad prospects of nanocatalysis-based anti-tumor immune-therapeutics.

Catechol-Isolated Atomically Dispersed Nanocatalysts for Self-Motivated Cocatalytic Tumor Therapy.

Nanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate-determining step in Fenton chemistry, which involves the transition of a high-valence metallic center (FeIII ) to a Fenton-active low-valence metallic center (FeII ), has hindered advances in nanocatalyst-based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field-effect-based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self-motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.

Anti-Acidification and Immune Regulation by Nano-Ceria-Loaded Mg-Al Layered Double Hydroxide for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H+ ) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient immune modulation and manipulating the accumulation of H+ that deteriorates bone damage. Herein, a highly effective immune modulatory nanocatalytic platform, nanoceria-loaded magnesium aluminum layered double hydroxide (LDH-CeO2 ), is proposed for enhanced immune modulation based on acid neutralization and metal ion inherent bioactivity. Specifically, the mild alkaline LDH initiates significant M2 repolarization of macrophages triggered by the elevated antioxidation effect of CeO2 via neutralizing excessive H+ in RA microenvironment, thus resulting in the efficient recruitment of regulatory T cell (Treg) and suppressions on T helper 17 cell (Th 17) and plasma cells. Moreover, the osteogenic activity is stimulated by the Mg ion released from LDH, thereby promoting the damaged bone healing. The encouraging therapeutic outcomes in adjuvant-induced RA model mice demonstrate the high feasibility of such a therapeutic concept, which provides a novel and efficient RA therapeutic modality by the immune modulatory and bone-repairing effects of inorganic nanocatalytic material.

Modulating the Structure and Composition of Single-Atom Electrocatalysts for CO2 reduction.

Electrochemical CO2 reduction reaction (eCO2 RR) is a promising strategy to achieve carbon cycling by converting CO2 into value-added products under mild reaction conditions. Recently, single-atom catalysts (SACs) have shown enormous potential in eCO2 RR due to their high utilization of metal atoms and flexible coordination structures. In this work, the recent progress in SACs for eCO2 RR is outlined, with detailed discussions on the interaction between active sites and CO2 , especially the adsorption/activation behavior of CO2 and the effects of the electronic structure of SACs on eCO2 RR. Three perspectives form the starting point: 1) Important factors of SACs for eCO2 RR; 2) Typical SACs for eCO2 RR; 3) eCO2 RR toward valuable products. First, how different modification strategies can change the electronic structure of SACs to improve catalytic performance is discussed; Second, SACs with diverse supports and how supports assist active sites to undergo catalytic reaction are introduced; Finally, according to various valuable products from eCO2 RR, the reaction mechanism and measures which can be taken to improve the selectivity of eCO2 RR are discussed. Hopefully, this work can provide a comprehensive understanding of SACs for eCO2 RR and spark innovative design and modification ideas to develop highly efficient SACs for CO2 conversion to various valuable fuels/chemicals.

Controlled Construction of Core-Shell Structured Prussian Blue Analogues towards Enhanced Oxygen Reduction.

Metal-organic frameworks-based electrocatalysts have been developed as highly desirable and promising candidates for catalyzing oxygen reduction reaction (ORR), which, however, usually need to be prepared at elevated temperatures and may suffer from the framework collapse in water environments, largely preventing its industrial application. Herein, this work demonstrates a facile low-temperature ion exchange method to synthesize Mn and Fe co-loaded Prussian blue analogues possessing core-shell structured frameworks and favorable water-tolerance. Among the catalysts prepared, the optimal HMPB-2.6Mn shows a high ORR electrocatalytic performance featuring a half-wave potential of 0.86 V and zinc-air battery power density of 119 mW cm-2 , as well as negligible degradation up to 60 h, which are comparable to commercial Pt/C. Such an excellent electrocatalytic performance is attributed to the special core-shell-like structure with Mn concentrated in outer shell, and the synergetic interactions between Mn and Fe, endowing HMPB-Mn with outstanding ORR activity and good stability.

Soybean Oil-Derived Lipids for Efficient mRNA Delivery.

The rapid progress in the development of COVID-19 mRNA vaccines during the initial year of the pandemic has highlighted the significance of lipid nanoparticles in therapeutic delivery. Various lipid types have been investigated for the effective delivery of mRNA, each with unique functions and versatile applications. These range from their use in cancer immunotherapy and gene editing to their role in developing vaccines against infectious diseases. Nonetheless, continued exploration of novel lipids and synthetic approaches is necessary to further advance the understanding and expand the techniques for optimizing mRNA delivery. In this work, new lipids derived from FDA-approved soybean oil are facilely synthesized and these are employed for efficient mRNA delivery. EGFP and Fluc mRNA are used to evaluate the delivery efficacy of the lipid formulations both in vitro and in vivo. Furthermore, organ-specific targeting capabilities are observed in certain formulations, and their outstanding performance is demonstrated in delivering Cre mRNA for gene editing. These results showcase the potential of soybean oil-derived lipids in mRNA delivery, offering utility across a broad spectrum of bioapplications.

Coupling Electrochemical Sulfion Oxidation with CO2 Reduction over Highly Dispersed p-Bi Nanosheets and CO2 -Assisted Sulfur Extraction.

We report herein an electrocatalytic CO2 reduction-coupled sulfion oxidation system for the co-productions of valuable formate and sulfur at much enhanced atom utilization. Specifically, an organic ligand-assisted two-step reconstruction approach has been developed to fabricate the highly dispersed p-Bi nanosheets (p-Bi NSs) for cathodic CO2 reduction reaction (CO2 RR), and meanwhile porous Co-S nanosheets (Co-S NSs) was applied for anodic sulfion oxidation reaction (SOR). Significantly high Faradaic Efficiencies of about 90 % for formate production by CO2 RR in a wide potential range from -0.6 V to -1.1 V, and excellent SOR performances including an ultra-low onset potential of about 0.2 V and recycle capacity of S2- in the 0.1 M and 0.5 M S2- solutions, have been simultaneously achieved. In the meantime, both the structure transformation of the catalysts and the reaction pathways are explored and discussed in detail. A two-electrode CO2 RR||SOR electrolyzer equipped with above electrocatalysts has been established, which features as low as about 1.5 V to run the electrolyzer at 100 mA cm-2 , manifesting extremely lowered electricity consumption in comparison to conventional CO2 RR system. Moreover, a sulfur separation approach has been proposed by using CO2 , which is efficient, environmentally friendly and cost effective with value-added NaHCO3 be obtained as the byproduct.

Nanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy.

Pro-tumoral macrophages in lung tumors present a significant challenge in immunotherapy. Here, we introduce a pH-responsive nanomedicine approach for activating anti-tumoral macrophages and dendritic cells. Using a layered double hydroxide nanosheet carrier, we co-deliver a T-type calcium channel inhibitor (TTA-Q6) and a CD47 inhibitor (RRX-001) into lung tumors. In the tumor acidic environment, TTA-Q6 is released, disrupting cancer cell calcium uptake, causing endoplasmic reticulum stress and inducing calreticulin transfer to the cell surface. Surface calreticulin activates macrophages and triggers dendritic cell maturation, promoting effective antigen presentation and therefore activating antitumor T cells. Simultaneously, RRX-001 reduces CD47 protein levels, aiding in preventing immune escape by calreticulin-rich cancer cells. In lung tumor models in male mice, this combined approach shows anti-tumor effects and immunity against tumor re-exposure, highlighting its potential for lung cancer immunotherapy.

Biomimetic inducer enabled dual ferroptosis of tumor and M2-type macrophages for enhanced tumor immunotherapy.

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment which promotes the formation of the immunosuppressive tumor microenvironment (ITME) through multiple mechanisms, severely counteracting the therapeutic efficacy of immunotherapy. In this study, a novel biomimetic ferroptosis inducer (D@FMN-M) capable of ITME regulation for enhanced cancer ferroptosis immunotherapy is reported. Upon tumor accumulation of D@FMN-M, the intratumoral mild acidity triggers the biodegradation of Fe-enriched nanocarriers and the concurrent co-releases of dihydroartemisinin (DHA) and Fe3+. The released Fe3+ is reduced to Fe2+ by consuming intratumoral glutathione (GSH), which promotes abundant free radical generation via triggering Fenton and Fe2+-DHA reactions, thus inducing ferroptosis of both cancer cells and M2-type TAMs. Resultantly, the anticancer immune response is strongly activated by the massive tumor-associated antigens released by ferroptositic cancer cells. Also importantly, the ferroptosis-sensitive M2-type TAMs will be either damaged or gradually domesticated to ferroptosis-resistant M1 TAMs under the ferroptosis stress, favoring the normalization of ITME and finally amplifying cancer ferroptosis immunotherapeutic efficacy. This work provides a novel strategy for ferroptosis immunotherapy of solid tumors featuring TAMs infiltration and immunosuppression by inducing dual ferroptosis of tumor cells and M2-type TAMs.