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.

Biomimetic-Structured Cobalt Nanocatalyst Suppresses Aortic Dissection Progression by Catalytic Antioxidation.

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.

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).

Single-Atom Catalysts with Isolated Cu1-N4 Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling.

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

Magnetothermal-activated gene editing strategy for enhanced tumor cell apoptosis.

Precise and effective initiation of the apoptotic mechanism in tumor cells is one of the most promising approaches for the treatment of solid tumors. However, current techniques such as high-temperature ablation or gene editing suffer from the risk of damage to adjacent normal tissues. This study proposes a magnetothermal-induced CRISPR-Cas9 gene editing system for the targeted knockout of HSP70 and BCL2 genes, thereby enhancing tumor cell apoptosis. The magnetothermal nanoparticulate platform is composed of superparamagnetic ZnCoFe2O4@ZnMnFe2O4 nanoparticles and the modified polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface, on which plasmid DNA can be effectively loaded. Under the induction of a controllable alternating magnetic field, the mild magnetothermal effect (42℃) not only triggers dual-genome editing to disrupt the apoptosis resistance mechanism of tumor cells but also sensitizes tumor cells to apoptosis through the heat effect itself, achieving a synergistic therapeutic effect. This strategy can precisely regulate the activation of the CRISPR-Cas9 system for tumor cell apoptosis without inducing significant damage to healthy tissues, thus providing a new avenue for cancer treatment.

Engineering lactate-modulating nanomedicines for cancer therapy.

Lactate in tumors has long been considered "metabolic junk" derived from the glycolysis of cancer cells and utilized only as a biomarker of malignancy, but is presently believed to be a pivotal regulator of tumor development, maintenance and metastasis. Indeed, tumor lactate can be a "fuel" for energy supply and functions as a signaling molecule, which actively contributes to tumor progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities for cancer treatment. However, the current approaches for regulating lactate homeostasis with available agents are still challenging, which is mainly due to the short half-life, low bioavailability and poor specificity of these agents and their unsatisfactory therapeutic outcomes. In recent years, lactate modulation nanomedicines have emerged as a charming and efficient strategy for fighting cancer, which play important roles in optimizing the delivery of lactate-modulating agents for more precise and effective modulation and treatment. Integrating specific lactate-modulating functions in diverse therapeutic nanomedicines may overcome the intrinsic restrictions of different therapeutic modalities by remodeling the pathological microenvironment for achieving enhanced cancer therapy. In this review, the most recent advances in the engineering of functional nanomedicines that can modulate tumor lactate for cancer therapy are summarized and discussed, and the fundamental mechanisms by which lactate modulation benefits various therapeutics are elucidated. Finally, the challenges and perspectives of this emerging strategy in the anti-tumor field are highlighted.

Ferrihydrite Nanoparticles Alleviate Rheumatoid Arthritis by Nanocatalytic Antioxidation and Oxygenation.

Oxidative stress and hypoxia are two key biochemical factors in the development of rheumatoid arthritis (RA). As both reactive oxygen species (ROS) and oxygen gas (O2) are oxygen-related chemicals, we suggest that a redox reaction converting ROS into O2 can mitigate oxidative stress and hypoxia concurrently, synergistically modulating the inflammatory microenvironment. In this work, ferrihydrite, a typical iron oxyhydroxide, is prepared in nanodimensions in which tetrahedrally coordinated Fe can form a composite catalytic center by coupling with an adjacent hydroxyl group, cooperatively facilitating H2O2 decomposition and O2 generation, presenting a high catalase-like activity. In the RA region, the nanomaterial catalyzes the conversion of excess H2O2 into O2, achieving both antioxidation and oxygenation favoring the alleviation of inflammation. Both cellular and in vivo experiments demonstrate the desirable efficacy of ferrihydrite nanoparticles for RA treatment. This work provides a methodology for the catalytic therapy of inflammatory diseases featuring both oxidative stress and hypoxia.

Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment.

The oral delivery of probiotics is commonly adopted for intestinal disease treatments in clinical settings; however, the probiotics suffer from a strong acidic attack in the gastric area and the low-efficiency intestinal colonization of naked probiotics. Coating living probiotics with synthetic materials has proven effective in enabling the adaption of bacteria to gastrointestinal environments, which, unfortunately, may shield the probiotics from initiating therapeutic responses. In this study, we report a copolymer-modified two-dimensional H-silicene nanomaterial (termed SiH@TPGS-PEI) that can facilitate probiotics to adapt to diverse gastrointestinal microenvironments on-demand. Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new light on the development of intelligent self-adaptive materials.

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.

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.

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.

Triple Regulations via Fe Redox Boosting Nitrate Reduction to Ammonia at Industrial Current Densities.

Electrochemical nitrate reduction reaction (NO3-RR) has promising prospects for green synthesis of ammonia and environmental remediation. However, the performance of catalysts at high current density usually suffers from the high energy barrier for the nitrate (NO3-) to nitrite (NO2-) and the competitive hydrogen evolution. Herein, we proposed a two-step relay mechanism through spontaneous redox reaction followed electrochemical reaction by introducing low-valence Fe species into Ni2P nanosheets to significantly enhance the NO3-RR performance at industrial current density. The existence of low-valence Fe species bypasses the NO3- to NO2- step through the spontaneous redox with NO3- to produce NO2- and Fe2O3, regulates the electronic structure of Ni2P to reduce the barrier of NO2- to NH3, thirdly prohibits the hydrogen evolution by consuming the excess active hydrogen through reduction of Fe2O3 to recover low-valence Fe species. The triple regulations via Fe redox during the two-step relay reactions guarantee the Fe-Ni2P@NF high ammonia yield of 120.1 mg h-1 cm-2 with Faraday efficiency of more than 90% over a wide potential window and a long-term stability of more than 130 h at ~1000 mA cm-2. This work provides a new strategy to realize the design and synthesis of nitrate reduction electrocatalysts at high current densities.

Anode-Electrolyte Interfacial Acidity Regulation Enhances Electrocatalytic Performances of Alcohol Oxidations.

The local acidity at the anode surface during electrolysis is apparently stronger than that in bulk electrolyte due to the deprotonation from the reactant, which leads to the deteriorated electrocatalytic performances and product distributions. Here, an anode-electrolyte interfacial acidity regulation strategy has been proposed to inhibit local acidification at the surface of anode and enhance the electrocatalytic activity and selectivity of anodic reactions. As a proof of the concept, CeO2-x Lewis acid component has been employed as a supporter to load Au nanoparticles to accelerate the diffusion and enrichment of OH- toward the anode surface, so as to accelerate the electrocatalytic alcohol oxidation reaction. As the result, Au/CeO2-x exhibits much enhanced lactic acid selectivity of 81 % and electrochemical activity of 693 mA⋅cm-2 current density in glycerol oxidation reaction compared to pure Au. Mechanism investigation reveals that the introduced Lewis acid promotes the mass transport and concentration of OH- on the anode surface, thus promoting the generation of lactic acid through the simultaneous enhancements of Faradaic and non-Faradaic processes. Attractively, the proposed strategy can be used for the electro-oxidation performance enhancements of a variety of alcohols, which thereby provides a new perspective for efficient alcohol electro-oxidations and the corresponding electrocatalyst design.

Nebulized Immunotherapy of Orthotopic Lung Cancer by Mild Magnetothermal-based Innate Immunity Activations.

Advances in adaptive immunity have greatly contributed to the development of cancer immunotherapy. However, its over-low efficacy and insufficient invasion of immune cells in the tumor tissue, and safety problems caused by cytokine storm, have seriously impeded further clinical application for solid tumor immunotherapy. Notably, the immune microenvironment of the lungs is naturally enriched with alveolar macrophages (AMs). Herein, we introduce a novel nebulized magnetothermal immunotherapy strategy to treat orthotopic lung cancer by using magnetothermal nanomaterial (Zn-CoFe2O4@Zn-MnFe2O4-PEG, named ZCMP), which can release iron ions via an acid/thermal-catalytic reaction to maximize the use of lung's immune environment through the cascade activations of AMs and natural killer (NK) cells. Nebulized administration greatly enhance drug bioavailability by localized drug accumulation at the lesion site. Upon mild magnetic hyperthermia, the released iron ions catalyze endogenous H2O2 decomposition to produce reactive oxygen species (ROS), which triggers the M1 polarization of AMs, and the resultant inflammatory cytokine IFN-ß, IL-1ß and IL-15 releases to activate c-Jun, STAT5 and GZMB related signaling pathways, promoting NK cells proliferation and activation. This innovative strategy optimally utilizes the lung's immune environment and shows excellent immunotherapeutic outcomes against orthotopic lung cancer.

Membrane-Free Electrocatalytic Co-Conversions of PBS Waste Plastics and Maleic Acid into High-Purity Succinic Acid Solid.

Plastic pollution, an increasingly serious global problem, can be addressed through the full lifecycle management of plastics, including plastics recycling as one of the most promising approaches. System design, catalyst development, and product separation are the keys in improving the economics of electrocatalytic plastics recycling. Here, a membrane-free co-production system was devised to produce succinic acid (SA) at both anode and cathode respectively by the co-electrolysis of polybutylene succinate (PBS) waste plastics and biomass-derived maleic acid (MA) for the first time. To this end, Cr3+-Ni(OH)2 electrocatalyst featuring much enhanced 1,4-butanediol (BDO) oxidation reaction (BOR) activity has been synthesized and the role of doped Cr has been revealed as an "electron puller" to accelerate the rate-determining step (RDS) in the Ni2+/Ni3+ cycling. Impressively, an extra-high SA production rate of 3.02 g h-1 and ultra-high apparent Faraday efficiency towards SA (FEapparent=181.5%) have been obtained. A carbon dioxide-assisted sequential precipitation approach has been developed to produce high-purity SA and byproduct NaHCO3 solids. Preliminary techno-economic analysis demonstrates that the reported system is economically profitable and promising for future industrial applications.

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.

Nebulized Therapy of Early Orthotopic Lung Cancer by Iron-Based Nanoparticles: Macrophage-Regulated Ferroptosis of Cancer Stem Cells.

Cancer stem cells (CSCs) within protumorigenic microlesions are a critical driver in the initiation and progression of early stage lung cancer, where immune cells provide an immunosuppressive niche to strengthen the CSC stemness. As the mutual interactions between CSCs and immune cells are increasingly recognized, regulating the immune cells to identify and effectively eliminate CSCs has recently become one of the most attractive therapeutic options, especially for abundant tumor-associated macrophages (TAMs). Herein, we developed a nebulized nanocatalytic medicine strategy in which iron-based nanoparticle-regulated TAMs effectively target CSC niches and trigger CSC ferroptosis in the early stage of lung cancer. Briefly, the iron-based nanoparticles can effectively accumulate in lung cancer microlesions (minimum 122 µm in diameter) through dextran-mediated TAM targeting by nebulization administration, and as a result, nanoparticle-internalized TAMs can play a predominant role of the iron factory in elevating the iron level surrounding CSC niches and destroying redox equilibrium through downregulating glucose-6-phosphate metabolite following their lysosomal degradation and iron metabolism. The altered microenvironment results in the enhanced sensitivity of CSCs to ferroptosis due to their high expression of the CD44 receptor mediating iron endocytosis. In an orthotopic mouse model of lung cancer, the initiation and progression of early lung cancer are significantly suppressed through ferroptosis-induced stemness reduction of CSCs by nebulization administration. This work presents a nebulized therapeutic strategy for early lung cancer through modulation of communications between TAMs and CSCs, which is expected to be a general approach for regulating primary microlesions and micrometastatic niches of lung cancer.

MnOOH-Catalyzed Autoxidation of Glutathione for Reactive Oxygen Species Production and Nanocatalytic Tumor Innate Immunotherapy.

The antioxidant system, signed with reduced glutathione (GSH) overexpression, is the key weapon for tumor to resist the attack by reactive oxygen species (ROS). Counteracting the ROS depletion by GSH is an effective strategy to guarantee the antitumor efficacy of nanocatalytic therapy. However, simply reducing the concentration of GSH does not sufficiently improve tumor response to nanocatalytic therapy intervention. Herein, a well-dispersed MnOOH nanocatalyst is developed to catalyze GSH autoxidation and peroxidase-like reaction concurrently and respectively to promote GSH depletion and H2O2 decomposition to produce abundant ROS such as hydroxyl radical (·OH), thereby generating a highly effective superadditive catalytic therapeutic efficacy. Such a therapeutic strategy that transforms endogenous "antioxidant" into "oxidant" may open a new avenue for the development of antitumor nanocatalytic medicine. Moreover, the released Mn2+ can activate and sensitize the cGAS-STING pathway to the damaged intratumoral DNA double-strands induced by the produced ROS to further promote macrophage maturation and M1-polarization, which will boost the innate immunotherapeutic efficacy. Resultantly, the developed simple MnOOH nanocatalytic medicine capable of simultaneously catalyzing GSH depletion and ROS generation, and mediating innate immune activation, holds great potential in the treatment of malignant tumors.

Magnetic-Manipulated NK Cell Proliferation and Activation Enhance Immunotherapy of Orthotopic Liver Cancer.

The immunotherapy of deep solid tumors in the human body, such as liver cancer, still faces great challenges, especially the inactivation and insufficient infiltration of immune cells in solid tumor microenvironment. Natural killer (NK) cells are gaining ever-increasing attention owing to their unique features and are expected to play an important role in the liver cancer immunotherapy. However, NK cells are severely insufficient and inactivated in solid liver tumor due to the highly immunosuppressive intratumor microenvironment, resulting in poor clinical therapeutic efficacy. Herein, we propose a mild magnetocaloric regulation approach using a magnetogenetic nanoplatform MNPs@PEI-FA/pDNA (MPFD), which is synthesized by loading a heat-inducible plasmid DNA (HSP70-IL-2-EGFP) on polyethyleneimine (PEI)- and folic acid (FA)-modified ZnCoFe2O4@ZnMnFe2O4 magnetic nanoparticles (MNPs) to promote the proliferation and activation of tumor-infiltrating NK cells under magnetic manipulation without the limitation of penetration depth for orthotopic liver cancer immunotherapy. The magnetothermally responsive MPFD serves as a magnetism-heat nanotransducer to induce the gene transcription of IL-2 cytokine in orthotopic liver tumor for NK cell proliferation and activation. Both in vitro and in vivo results demonstrate that the remote mild magnetocaloric regulation (∼40 °C) by MPFD initiates the HSP70 promoter to trigger the overexpression of IL-2 cytokine for subsequent secretion, leading to in situ expansion and activation of tumor-infiltrating NK cells through the IL-2/IL-2 receptor (IL-2R) pathways and the resulting prominent tumor inhibition. This work not only evidences the great potential of magnetogenetic nanoplatform but also reveals the underlying proliferation and activation mechanism of NK cells in liver cancer treatment by magnetogenetic nanoplatform.

Iodinene Nanosheet-to-Iodine Molecule Allotropic Transformation for Antibiosis.

Iodine, as a typical haloid element in group VIIA, has been extensively applied as antiseptics clinically, thanks to its effective and wide-spectrum antimicrobial activity against bacteria, fungi, and viruses. Nevertheless, current iodic sterilizing agents are still limited to topical applications such as instrument sterilization and treatments of skin or mucous membrane infection due to its unsatisfactory stability and biocompatibility. Here, we propose an emerging two-dimensional iodine nanomaterial (noted as iodinene) for the treatment of infection diseases in vivo. Iodinene nanosheets were fabricated by a facile and environmentally friendly approach via sonication-assisted liquid exfoliation, which present an intriguing layered structure and negligible toxicity. The as-synthesized iodinene would experience an in situ allotropic transformation spontaneously to release active HIO and I2 molecules by reacting with H2O2 in the infectious microenvironment. By the in situ production of active HIO and I2 molecules via allotropic transformation, iodinene presents enhanced antibacterial efficacy against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In vivo outcome demonstrates the desirable antibacterial efficacy of iodinene in treating bacterial wound infection and pneumonia. This study thus offers an alternative to conventional sterilizing agents against hard-to-treat bacterial infections.