Search

Therapeutic cancer vaccines are among the first FDA‐approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph‐node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated‐DCs homing from the periphery to the LNs, an injectable hydrogel‐based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated‐DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six‐fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN‐resident APCs via the "One‐to‐Many" strategy (One Migrated‐DC corresponding to Many LN‐resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation. [ABSTRACT FROM AUTHOR]

In order to explore the crystallization behavior of Co‐doped amorphous manganese dioxide(Co‐doped AMO) and to investigate the electrochemical properties of its different crystallization products as cathodes for aqueous zinc ion batteries. In this work, the effects of heat treatment temperature on the microstructure and phase composition of Co‐doped AMO and their electrochemical properties of Zn‐MnO2 battery cathode materials are systematically investigated. The results show that Co‐doping increases the crystallization temperature of pure AMO. When the heat treatment temperature is 400 °C, Co‐doped AMO is amorphous. At 500 and 550 °C, part of the Co‐doped AMO crystallizes into tetragonal spinel structured (Co, Mn)(Co, Mn)2O4 material between MnCo2O4 and Mn3O4. At 650 °C, the crystallized product is completely nano‐α‐Mn(Co)O2 crystal. The maximum discharge specific capacities and the retention rate after 100 cycles of the samples at 100 mA g−1 are 325.40 mAh g−1, 86.88%; 217.00 mAh g−1, 13.94%; 186.68 mAh g−1, 41.01%; and 149.03 mAh g−1, 31.27% for the unheated and 400, 550, 650 °C heat‐treated samples, respectively. It is proved that the Co‐doped AMO without heat treatment is superior to the partially or fully crystallized materials in terms of comprehensive performance and cost as cathode materials for AZIB. [ABSTRACT FROM AUTHOR]

Rare‐earth (RE) silicates environmental barrier coatings (EBCs) are prone to accelerate failure resulted from molten calcium–magnesium–aluminum silicate (CMAS), which presents significant challenges to the design and development of durable EBCs. In this study, X1‐Gd2SiO5 and X2‐Er2SiO5 coatings were explored on their corrosion resistance to CMAS melts with different Ca/Si ratios (1.1, 0.75, 0.64, and 0.42) at 1350°C for 25 and 50 h, respectively. Results showed that with the Ca/Si ratio increasing, CMAS viscosity decreased and a more intense corrosion reaction with coatings occurred. Garnet phase was only observed in X2‐Er2SiO5 coating corroded by CMAS with high Ca/Si ratios, which could be beneficial for improving corrosion resistance. The X2‐Er2SiO5 phase, which is composed of [SO4] and [REO6]/[REO7] polyhedrons, exhibits better corrosion resistance due to its more stable crystal structure, lower reactivity with CMAS, and the radius difference between the RE ions and Ca2+. [ABSTRACT FROM AUTHOR]

Immobilized Pd‐catalyzed Suzuki‐Miyaura coupling under continuous‐flow conditions using a packed‐bed reactor, representing an efficient, automated, practical, and safe technology compared to conventional batch‐type reactions. The core objective of this study is the development of an active and durable catalyst. In contrast to supported Pd nanoparticles, the attachment of Pd complexes onto solid supports through well‐defined coordination sites is considered a favorable approach for preparing highly dispersed and stabilized Pd species. These species can be directly employed in various flow reactions without the need for pre‐treatment. This concept paper explores recent achievements involving the application of immobilized Pd complexes as precatalysts for continuous‐flow Suzuki‐Miyaura coupling. Our focus is to elucidate the significance of the designed catalyst structures in relation to their catalytic performance under flow conditions. Additionally, we highlight various reaction systems and catalyst packing methods, emphasizing their crucial roles in establishing a practical synthesis process. [ABSTRACT FROM AUTHOR]

Precise and efficient regulation of microglia is vital for ischemic stroke therapy and prognosis. The infiltration of neutrophils into the brain provides opportunities for regulatory drugs across the blood–brain barrier, while hindered by neutrophil extracellular traps (NETs) and targeted delivery of intracerebral drugs to microglia. This study reports an efficient neutrophil hijacking nanoplatform (referred to as APTS) for targeted A151 (a telomerase repeat sequence) delivery to microglia without the generation of NETs. In the middle cerebral artery occlusion (MCAO) mouse model, the delivery efficiency to ischemic stroke tissues increases by fourfold. APTS dramatically reduces the formation of NETs by 2.2‐fold via reprogramming NETosis to apoptosis in neutrophils via a reactive oxygen species scavenging‐mediated citrullinated histone 3 inhibition pathway. Noteworthy, A151 within neutrophils is repackaged into apoptotic bodies following the death pattern reprogramming, which, when engulfed by microglia, polarizes microglia to an anti‐inflammatory M2 phenotype. After four times treatment, the cerebral infarction area in the APTS group decreases by 5.1‐fold. Thus, APTS provides a feasible, efficient, and practical drug delivery approach for reshaping the immune microenvironment and treating brain disorders in the central nervous system. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. Cancer cells can undergo programmed cell death including ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis which are find to have intrinsic relationships with host antitumor immune response. However, direct use of cell death inducers or regulators may bring about severe side effects that can also be rapidly excreted and degraded with low therapeutic efficacy. Nanomaterials are able to carry them for long circulation time, high tumor accumulation and controlled release to achieve satisfactory therapeutic effect. Nowadays, a large number of studies have focused on nanomedicines‐based strategies through modulating cell death modalities to potentiate antitumor immunity. Herein, immune cell types and their function are first summarized, and state‐of‐the‐art research progresses in nanomedicines mediated cell death pathways (e.g., ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis) with immune response provocation are highlighted. Subsequently, the conclusion and outlook of potential research focus are discussed. [ABSTRACT FROM AUTHOR]

Infections caused by Enterobacterales producing New Delhi Metallo‐β‐lactamases (NDMs), Zn(II)‐dependent enzymes hydrolyzing carbapenems, are difficult to treat. Depriving Zn(II) to inactivate NDMs is an effective solution to reverse carbapenems resistance in NDMs‐producing bacteria. However, specific Zn(II) deprivation and better bacterial outer membrane penetrability in vivo are challenges. Herein, authors present a pathogen‐primed liposomal antibiotic booster (M‐MFL@MB), facilitating drugs transportation into bacteria and removing Zn(II) from NDMs. M‐MFL@MB introduces bismuth nanoclusters (BiNCs) as a storage tank of Bi(III) for achieving ROS‐initiated Zn(II) removal. Inspired by bacteria‐specific maltodextrin transport pathway, meropenem‐loaded BiNCs are camouflaged by maltodextrin‐cloaked membrane fusion liposome to cross the bacterial envelope barrier via selectively targeting bacteria and directly outer membrane fusion. This fusion disturbs bacterial membrane homeostasis, then triggers intracellular ROS amplification, which activates Bi(III)‐mediated Zn(II) replacement and meropenem release, realizing more precise and efficient NDMs producer treatment. Benefiting from specific bacteria‐targeting, adequate drugs intracellular accumulation and self‐activation Zn(II) replacement, M‐MFL@MB rescues all mice infected by NDM producer without systemic side effects. Additionally, M‐MFL@MB decreases the bacterial outer membrane vesicles secretion, slowing down NDMs producer's transmission by over 35 times. Taken together, liposomal antibiotic booster as an efficient and safe tool provides new strategy for tackling NDMs producer‐induced infections. [ABSTRACT FROM AUTHOR]

The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4‐based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS‐DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4‐PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4‐PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy. [ABSTRACT FROM AUTHOR]

Herein, amorphous manganese dioxide (AMO) is prepared by the liquid‐phase coprecipitation method, the effect of heat treatment temperature on the microstructure, and phase composition of AMO and the electrochemical properties as cathode materials for aqueous Zn–MnO2 batteries are investigated. The results show that the AMO didn't crystallize at 250 °C, but its structure stability increases. When the temperature is 350 and 400 °C, part of the AMO crystallizes into rod‐shaped nano‐α‐MnO2 crystals. At 540 °C, the products crystallize into nano‐α‐MnO2 crystals. Continuing to increase the temperature to 650 °C, the structural stability of the products is further improved. Heat treatment leads to reduced specific surface area and porosity of the material, which in turn leads to reduced specific capacity and cycling stability. In addition, the heat‐treated products show a sharp drop in capacity during the discharge process; this was because the volume change caused by the irreversible phase change of the electrode material is difficult to release in the anisotropic crystal, resulting in the collapse of the structure. This study shows that unheated AMO is better than heat‐treated AMO as a cathode material for aqueous Zn–MnO2 battery cathode material in terms of overall performance and cost. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Radiotherapy is a mainstay treatment for malignant tumors in clinical practice. However, enhancing radiation damage to tumor cells meanwhile sparing normal tissues is still a great challenge in radiotherapy. Nanomaterials with high atomic number (Z) values are promising radiosensitizers by promoting the radiation energy deposition in irradiated tumor cells, thus enhancing the therapeutic ratio of radiotherapy. In this review, we described the mechanisms of high‐Z element based‐radiosensitizers and systematically summarized the recent progress on high‐Z metal‐based nanomaterials, including high‐Z metal‐based nanoparticles, high‐Z metal‐based nanoscale metal‐organic frameworks and high‐Z metal‐doping nanomaterials. Finally, further potential and challenges in this field were discussed. [ABSTRACT FROM AUTHOR]

Fast neutron and X‐ray imaging are considered complementary nondestructive detection technologies. However, due to their opposite cross‐sections, development of a scintillator that is sensitive to both fast neutrons and X‐rays within a single‐material framework remains challenging. Herein, an organic–inorganic hybrid perovskite (C4H9NH3)2PbBr4 (BPB) is demonstrated as a scintillator that fully meets the requirements for both fast neutron and X‐ray detection. The hydrogen‐rich organic component acts as a fast neutron converter and produces detectable recoil protons. The heavy atom‐rich inorganic fraction efficiently deposits the energy of charged recoil protons and directly provides a large X‐ray cross‐section. Due to the synergy of these organic and inorganic components, the BPB scintillator exhibits high light yields (86% of the brightness of a commercial ZnS (Ag)/6LiF scintillator for fast neutrons; 22 000 photons per MeV for X‐rays) and fast response times (τdecay = 10.3 ns). More importantly, energy‐selective fast neutron and X‐ray imaging are also demonstrated, with high resolutions of ≈1 lp mm−1 for fast neutrons and 17.3 lp mm−1 for X‐rays; these are among the highest resolution levels for 2D perovskite scintillators. This study highlights the potential of 2D perovskite materials for use in combined fast neutron and X‐ray imaging applications. [ABSTRACT FROM AUTHOR]

Amplifying intracellular oxidative stress by organelle‐targeted reactive oxygen species (ROS) production combined with tumor cell‐specific gene disruption is a promising strategy for tumor treatment. However, due to the vulnerability of CRISPR/Cas9 ribonucleoproteins (RNPs) to ROS, co‐delivery of CRISPR/Cas9 RNPs and ROS generators to enhance the sensitivity of tumor cells to oxidative stress remains challenging. Herein, a cascade‐responsive "oxidative stress amplifier" (named DR‐TAF‐pHT/FA) is proposed, which can successively respond to cathepsin B, localized laser irradiation and ATP to generate ROS on the lysosomal membrane of tumor cells and release Cas9/sgNrf2 RNPs for efficient gene disruption. It is demonstrated that, under near infrared (NIR) irradiation, DR‐TAF‐pHT/FA achieves targeted rupture of lysosomal membranes, inducing significant intracellular oxidative stress. Meanwhile, due to the protective function of TAF coating (TA‐Fe3+ coordination self‐assembled networks), Cas9/sgNrf2 RNPs can safely escape into the cytoplasm and be released in response to ATP, further amplifying oxidative stress and promoting tumor cell apoptosis through efficient Nrf2 gene disruption. Treatment with DR‐TAF‐pHT/FA + NIR significantly improves tumor ablation efficiency and extends median survival time (over 70 days) in Hela xenograft models. This "oxidative stress amplifier" provides a new paradigm for multimodal and synergistic tumor therapy through precise lysosomal membrane bursting together with efficient Nrf2 gene disruption. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a progressive histological manifestation that happens in almost all chronic liver diseases. An unabated liver fibrosis may eventually develop into liver cirrhosis or hepatocellular carcinoma. Yet, the strategy for reversal of liver fibrosis is still limited. Herein, a biomimetic nano‐regulator (P‐ZIF8‐cirDNAzyme) is developed to affect both collagen synthesis and degradation in liver to remodel collagen microenvironment. It is found that Zn (II) interference can efficiently inhibit collagen synthesis in activated hepatic stellate cells (aHSC) by inactivating proline 4 hydroxylase and affecting many fibrosis‐related signaling pathways. Meanwhile, Zn (II)‐dependent circular DNAzymes (cirDNAzymes) are used to efficiently silence tissue inhibitors of metalloproteinase‐1, accelerating the degradation of collagen. They act in concert to recover the balance between collagen deposition and degradation. Additionally, ZIF‐8‐cirDNAzyme is coated by platelet membrane (PM) for precisely targeting aHSC via PM's inflammatory tropism and CD62p–CD44 interaction. In carbon tetrachloride‐induced fibrotic mice, P‐ZIF‐8‐cirDNAzyme shows a potent anti‐fibrotic effect, greatly reducing the expression of collagen by 73.12% and restoring liver function nearly to normal. This work proposes a prospective platform enabling ion interference and gene silencing, collectively acting in aHSC for reversal of liver fibrosis. [ABSTRACT FROM AUTHOR]

Given that heterogeneous palladium‐catalyzed C−C bond formation reactions under continuous‐flow conditions are well suited for the efficient and safe production of pharmaceuticals and functional materials, the development of active and durable catalysts for this purpose is a matter of high practical significance. Here, a previously established molecular convolution methodology was used to synthesize catalysts for Suzuki‐Miyaura coupling under flow conditions by blending convoluted polymeric palladium catalysts (prepared from copolymers of 4‐vinylpyridine and 4‐tert‐butylstyrene) and crosslinked polymeric auxiliary materials (prepared from copolymers of divinylbenzene and 4‐tert‐butylstyrene). The optimal catalyst exhibited high performance and durability and allowed numerous biaryl products such as liquid‐crystalline materials, organic electroluminescent materials, and pharmaceuticals to be continuously synthesized with turnover frequencies of up to 238 h−1. In a demonstration of practical utility, the developed catalytic system was used for the continuous synthesis of two pharmaceuticals (felbinac and fenbufen) in water as the sole solvent. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second most common cause of cancer incidence worldwide. Oral drug delivery systems (ODDS) have shown great promise for CRC therapy, but the delivery efficiency is still challenged by the dense intestinal mucus barrier and nonspecific interception of abnormally proliferated pathogenic bacteria. Herein, self‐thermophoretic nanoparticles (CTPB) is presented to enhance intestinal mucus penetration and reduce pathogenic bacteria interception in CRC for efficient drug delivery. The nanoplatform introduces hollow mesoporous copper sulfide and is asymmetrically sprayed with titanium dioxide as the self‐thermophoretic matrix. Based on the close relationship between pathogenic bacteria and CRC, the nanoplatform is camouflaged by the biomimetic membrane of Staphylococcus aureus to precisely anchor in the intestinal segment of CRC. After near‐infrared laser irradiation, CTPB can effectively increase the intestinal mucus penetration efficiency by 2.7 folds, and decrease the pathogenic bacterial interception by 3.5 folds via the self‐thermophoretic propulsion force. In orthotopic CRC‐bearing mice, CTPB vastly improved the drug delivery efficiency to CRC after oral administration, thus showing a 99.4% antitumor rate after three weeks of treatment, which provides new insight into oral drug delivery for CRC therapy. [ABSTRACT FROM AUTHOR]

With the increasing service temperature of aeroengines, the development of thermal/environmental barrier coatings (T/EBCs) has been considered to be a great challenge, which requires high‐temperature stability and excellent thermal and mechanical properties. In this work, high‐entropy design was adopted to change the crystal structure of rare‐earth monosilicates used for T/EBCs. The microstructure evolution, thermal and mechanical properties of the plasma‐sprayed (Lu0.25Yb0.25Er0.25Y0.25)2SiO5 and (Lu0.2Yb0.2Er0.2Ho0.2Y0.2)2SiO5 coatings before and after thermal aging at 1350°C for 50 h were investigated. Results showed that the as‐sprayed coatings exhibited dense structure with amorphous and decomposed phases. The change of microstructure like amorphous crystallized and defect healing occurred after thermal aging, which had obvious influence on thermomechanical properties. Compared with single‐component RE2SiO5 (RE = Yb, Er, Y) coatings, the thermal‐aged high‐entropy coatings exhibited lower thermal conductivity, similar thermal expansion coefficient, and better toughness. The work will provide a foundation for the design and application of T/EBCs materials. [ABSTRACT FROM AUTHOR]

The clinical outcomes of programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) blockade are usually limited by the multiple immune evasion mechanism of the tumor, as well as the immune storm caused by "off‐target" effects of the PD‐1/PD‐L1 antibody. Here, a previously unknown strategy is proposed to synergize the "Ca2+ interference" mediated M2‐like tumor‐associated macrophages (TAM) re‐education and Ca2+‐activating locally PD‐L1 depletion for immunotherapy. The authors discover that calcium‐containing nanoparticles can induce significant "Ca2+ interference" effect and simultaneously reset TAM toward the M1 phenotype through activation of multiple inflammation‐related signaling pathways, as well as NLRP3 inflammasomes, and promoting in situ tumor‐associated antigen release. In addition, a circular aptamer‐DNAzyme conjugate (cAD) is designed with a tumor‐targeting ability and its catalytic shear activity can be specifically activated by Ca2+, which reduces potential autoimmune‐like disorders of PD‐L1 antibody. By simply integrating the ultra‐high pH‐sensitive calcium peroxide nanoparticles with cAD into one nanosystem, it is demonstrated that the nanosystem not only arrest primary tumor progression and lung metastasis but also provides a long‐term immunological memory, which can protect against tumor rechallenge. Therefore, this work provides an attractive strategy for boosting tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Efficient nuclear DNA damage and release is highly recommended to improve the photodynamic immunotherapy by eliciting innate immune response yet remains challenging. Herein, an intracellular self‐assembly driven nucleus‐targeted photo‐immune stimulator (PIS) with chromatin decompaction function is reported for innate and adaptive antitumor immunity co‐activation. The PIS consists of vorinostat (SAHA)‐loaded manganese‐porphyrin metal‐organic framework (Mn (III)‐TCPP MOF) with further modification of AS1411 aptamer. The PIS can be efficiently internalized by tumor cells and disassembled under the intracellular overexpressed glutathione (GSH). Notably, the released AS1411 is able to be self‐assembled with photosensitizer TCPP in situ within cells, driving nucleus‐targeted delivery of TCPP; meanwhile, the loaded SAHA can induce chromatin decompaction, cooperatively promoting TCPP‐mediated photodynamic nuclear DNA damage and cytosolic release under laser irradiation. In addition, the released manganese ions (Mn2+) further enhance the cytosolic DNA/cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon gene (STING) pathway mediated innate immunity, which synergizes with PDT‐induced immunogenic cell death to achieve co‐activation of innate and adaptive immunity. Compared to traditional PDT, the self‐assembly driven nucleus‐targeted PDT system with chromatin decompaction show significantly enhanced efficacy for inhibiting primary tumor growth and distant metastasis in several xenograft tumor models, mechanistically by promoting the maturation of dendritic cells and tumor infiltration of natural killer cell, cytotoxic T lymphocytes. [ABSTRACT FROM AUTHOR]

Carbon‐nitrogen bond formation is an important method on both laboratory and industrial scales because it realizes the production of valuable pharmaceuticals, agrochemicals, and fine chemicals. Direct reductive N‐alkylation of amines with carbonyl compounds via intermediary imine compounds, especially under catalytic hydrogenation conditions, is one of the most convenient, economical, and environmentally friendly methods for this process. Here we report a novel palladium species on zirconia having specific activity towards hydrogenation of imines but other carbonyl groups remaining intact. The present catalytic property offers a practical synthetic method of functionalized secondary amines by reductive N‐alkylation under mild conditions with high atom‐efficiency. Mechanistic studies revealed that the catalytically active species is the palladium cluster, which is generated in situ from molecular palladium complexes on the support by exposure to atmospheric hydrogen. These fundamental findings are expected to progress in developing novel cluster catalysts for chemical processes directed towards a sustainable society. [ABSTRACT FROM AUTHOR]

Aims: Based on the complex pathological environment of perioperative stroke, the development of targeted therapeutic strategies is important to control the development of perioperative stroke. Discussions: Recently, great progress has been made in nanotechnology, and nanodrug delivery systems have been developed for the treatment of ischemic stroke. Conclusion: In this review, the pathological processes and mechanisms of ischemic stroke during perioperative stroke onset were systematically sorted. As a potential treatment strategy for perioperative stroke, the review also summarizes the multifunctional nanodelivery systems based on ischemic stroke, thus providing insight into the nanotherapeutic strategies for perioperative stroke. [ABSTRACT FROM AUTHOR]

X‐ray imaging technology covers a wide range of applications in the medical, industrial, and scientific research fields. Highly sensitive, flexible, and cost‐effective scintillation screens are of great importance for X‐ray imaging applications. In this paper, manganese (II) activated 2D butylammonium lead bromide perovskite, namely BA2PbBr4:Mn (II), is demonstrated as a highly efficient and low‐cost X‐ray scintillator. The appropriate amount of Mn (II) dopant can act as an activator for achieving the optimization of luminescence performance through efficient energy transfer. This produces a large Stokes shift thus almost eliminates the effect of self‐absorption. As a result, the optimal BA2PbBr4:10% Mn (II) perovskite scintillator demonstrates an ultrahigh sensitivity for X‐ray, with a high X‐ray scintillation light yield of up to 85 ± 5 photons keV−1 and low detection limits of 16 nGyair s−1 at the signal‐to‐noise ratio (SNR) of 3. Well‐resolved X‐ray images of several planar and nonplanar objects are obtained using a flexible large‐dimensional scintillation screen fabricated by blade‐coating strategy, featuring high spatial resolution of 10.7 lp mm−1 at modulation transfer function = 0.2. These results indicate that Mn (II) activated BA2PbBr4 perovskite with remarkable scintillation performances can serve as a highly promising scintillator for commercial high‐resolution X‐ray imaging applications. [ABSTRACT FROM AUTHOR]

Despite the promise of tumor starvation therapies, they are often associated with nonspecific and incomplete energy blockade. Here, a novel paradigm of starvation therapy is proposed to synergize the "Zn2+ interference"‐mediated glycolysis inhibition and Zn2+‐activating GLUT1 (Glucose transporter 1) tumor specific depletion for systematic energy exhaustion. It is discovered that ZIF‐8 (zinc imidazolate metal–organic frameworks) can induce abrupt intracellular Zn2+ elevation preferentially in melanoma cells, and then achieve effective glycolysis blockade through "Zn2+ interference"‐triggered decrease of NAD+ and inactivation of GAPDH, making it a powerful tumor energy nanoinhibitor. Meanwhile, Zn2+‐activating DNAzymes for specifically cleaving GLUT1 mRNA is designed. This DNAzyme can only be activated under intracellular Zn2+ overloading, and then directionally cut off glucose supply, which further restrains the adaptive up‐regulation of glycolytic flux after glycolysis inhibition in tumors. Afterward, DNAzymes are loaded in ZIF‐8 concurrently tethered by hyaluronic acid (HA), constructing a "nanoenabled energy interrupter ". Such a rational design presents a preferential accumulation tendency to tumor sites due to the active CD44‐targeting mechanisms, specifically achieves remarkable systematic energy exhaustion in melanoma cells, and affords 80.8% in tumor growth suppression without systemic toxicity in vivo. This work verifies a fascinating therapeutic platform enabling ion interference‐inductive starvation strategy for effective tumor therapy. [ABSTRACT FROM AUTHOR]

Following ischemic stroke, brain‐resident activated microglia and peripherally infiltrated inflammatory cells create a complicated and overactivated brain immune microenvironment, which causes neuron death and dramatically hinders neurological functional recovery. Herein, an engineering CXCL12 biomimetic decoy‐integrated versatile immunosuppressive nanoparticle (VIN) for management of the overactivated brain immune microenvironment is reported. The shell of VIN (membrane of CXCR4 overexpressed mesenchymal stem cells), can not only improve the homing of nanoparticles to the cerebral ischemic lesions, but also efficiently adsorb and neutralize CXCL12 to cut off infiltration of peripheral‐neutrophils and mononuclear macrophages. The loaded A151 (cGAS inhibitor, telomerase repeat sequences) can inhibit cGAS‐STING pathway in microglia, leading to microglia polarization toward an anti‐inflammatory M2‐like phenotype. Interestingly, A151 can be efficiently loaded onto the polydopamine nanospheres (PDA, the core of VIN) through the bridge of Zn2+. In the inflammatory site, PDA is oxidized by reactive oxygen species (ROS), with the disappearance of Zn2+ complexation effect, and then A151 realizes a controlled release. In a model of rat ischemic stroke, VIN integrates inflammation tropism, peripherally inflammatory cells filtrate, brain‐resident activated microglia polarization, as well as, ROS scavenging, exerting outstanding therapeutic effects on ameliorating the mortality, reducing the infarct volume, and protecting neurogenic functions of neurons. [ABSTRACT FROM AUTHOR]

A fundamental challenge in probiotic therapy is effective delivery and rapid colonization of probiotics; however, the physiological structure of probiotic spores provides an interesting idea to address this problem. Herein, the spore coat is innovatively prepared into a type of versatile spore coat nanomaterial (CN) which is subsequently anchored to the surface of probiotics to form CN‐coated probiotics. The CN retains the characteristics of high resistance and natural affinity of spore coats, which serve as the "armor" for the enhancement of the probiotics delivery. Moreover, CN is beneficial for the explosive proliferation and competitive colonization of probiotics. Notably, it is found that not only CN used solely has good anti‐inflammatory effect, but also it can significantly improve the functions of probiotics such as microbiome regulation, gut barrier integrity and tumor prevention. This work provides a simple and universal strategy that may guide the development of nanomaterial and material‐based microecological agents. [ABSTRACT FROM AUTHOR]

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer‐associated fibroblasts (CAFs) responsive honeycomb‐like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs‐loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor. [ABSTRACT FROM AUTHOR]

Despite the potential of drug‐loaded scaffolds for tumor recurrence and metastasis (TRM) postoperation, their therapeutic benefits are limited by marked immunosuppressive tumor microenvironment (ITME) and drug‐related untargeted toxicity. Herein, an innovative implantable bioresponsive nanoarray is developed to overcome the above limitations. Chemotherapeutics doxorubicin (DOX) and the epigenetic modulator JQ1 are coloaded into tumor‐targeting nanoparticles (HP‐DOX/JQ1 NPs), which are then linked up through a bio‐responsive linker to construct the nanoarray loading with another part of JQ1 (DOX/JQ1‐IBRN). Under high level of H2O2 in TME, the implanted DOX/JQ1‐IBRN disaggregates and release JQ1 while generating small‐sized HP‐DOX/JQ1 NPs for realizing ITME modulation and tumor‐targeting therapy. JQ1 selectively blocks programmed death‐ligand 1 (PD‐L1) mediated immune evasion and reduces regulatory T cells (Tregs)/‐disruptive effect to facilitate immunopositivity. HP‐DOX/JQ1 NPs destroy residual tumor precisely and trigger gasdermin E (GSDME)‐dependent pyroptosis, further enhancing the number and functions of tumor‐infiltrating T lymphocytes for antitumor immunity. It is demonstrated that DOX/JQ1‐IBRN prevents post‐surgical TRM and prolongs survival in multiple murine tumor models with negligible toxicity. This cooperation in tumor accurate pyroptosis and ITME conversion through the implantable nanoarray (a simple, valid, and safe scaffold) is expected to provide crucial insights for post‐surgical treatment. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) have attracted increasing attention as tumour biomarkers due to their unique biological property. However, conventional methods for EV analysis are mainly based on bulk measurements, which masks the EV‐to‐EV heterogeneity in tumour diagnosis and classification. Herein, a localized fluorescent imaging method (termed Digital Profiling of Proteins on Individual EV, DPPIE) was developed for analysis of multiple proteins on individual EV. In this assay, an anti‐CD9 antibody engineered biochip was used to capture EV from clinical plasma sample. Then the captured EV was specifically recognized by multiple DNA aptamers (CD63/EpCAM/MUC1), followed by rolling circle amplification to generate localized fluorescent signals. By‐analyzing the heterogeneity of individual EV, we found that the high‐dimensional data collected from each individual EV would provide more precise information than bulk measurement (ELISA) and the percent of CD63/EpCAM/MUC1‐triple‐positive EV in breast cancer patients was significantly higher than that of healthy donors, and this method can achieve an overall accuracy of 91%. Moreover, using DPPIE, we are able to distinguish the EV between lung adenocarcinoma and lung squamous carcinoma patients. This individual EV heterogeneity analysis strategy provides a new way for digging more information on EV to achieve multi‐cancer diagnosis and classification. [ABSTRACT FROM AUTHOR]

The reactive oxygen species (ROS) play a decisive role in sonodynamic therapy (SDT). However, hypoxic microenvironment of tumors and short lifetime of ROS limit the implementation of SDT. In this work, an ultrasound (US)‐triggered ROS sustained supplier based on open source and reduce expenditure strategy was constructed. The mesoporous titanium dioxide nanoparticles (MTN) were used as carriers and sonosensitizers, to load US‐responsive perfluoropentane (PFP) and bleomycin (BLM), a blocking agent to reduce ROS scavenging. Thereafter, nanoparticles were wrapped by red blood cell membrane (RBCm) with TKD modification (TKD@RMPB). Under US irradiation, MTN disintegrated into small TiO2 nanoparticles to release PFP and BLM. PFP effectively supplied O2 to enhance ROS generation. Furthermore, BLM reduced the activity of SOD enzyme so that ROS clearance would decrease. This dual role contributed ROS explosive accumulation in tumor cells. In vitro results showed the ROS level of TKD@RMPB group was 3.62 times that of MTN group. Compared with MTN, the proportion of DNA damage in TKD@RMPB group increased by 2.23 times. Moreover, in vivo results indicated that TKD@RMPB could significantly reduce pulmonary fibrotic lesions caused by BLM, suggesting that TKD@RMPB realized simultaneous chemotherapy and SDT for HT‐29 colon cancer with high efficiency and low toxicity. [ABSTRACT FROM AUTHOR]

Some manganese‐based nanomaterials quench the fluorescence of photosensitizers, which strongly quenches fluorescence emission and suppresses reactive oxygen species (ROS) production due to the photo‐induced charge transfer from the excited photosensitizer to nanomaterials. In this study, to overcome these disadvantages, amorphous porous manganese phosphate (MnP) nanoparticles are used for loading indocyanine green (ICG), and a broader ICG absorbance width instead of weakened fluorescence profile is observed, resulting in higher stability and phototherapy efficiency under 808 nm irradiation. Moreover, autophagy inhibition obviously weakens the ICG‐mediated phototherapy to breast cancer cells. On this foundation, an autophagy promoter rapamycin (RAPA) and ICG are co‐loaded into the MnP nanoparticles, and further decorated with biocompatible poly(glutamic acid). As expected, this stable nanoplatform released 80.0±4.1% agents at low pH compared to that 32.0±4.8% at normal pH, indicating a clear pH‐responsive release profile. Uniting phototherapy with autophagy promoter by this system is found to achieve synergistic outcomes as evidenced by the smaller relative tumor volume of 1.8±0.4. Overall, this work provides the first photo‐stable manganese‐based nanomaterial without fluorescence quenching profile for achieving multiple desirable therapeutic performances. [ABSTRACT FROM AUTHOR]

The article titled "Front Cover: Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor‐designed ZnFe2O4‐based nanosystem" by Hou et al. discusses the construction of ZnFe2O4 nanoparticles loaded with low-dose paclitaxel (PTX) and encapsulated with cancer cell membrane (CCM). These nanoparticles are designed to respond to the high level of GSH in the tumor cytoplasm, releasing Fe3+, Zn2+, and PTX. This release stimulates anti-tumor immunity by enhancing the cGAS/STING pathway. The authors provide a detailed analysis of their findings and propose that this nanosystem could be used for tumor immunotherapy. [Extracted from the article]

Combination of PdCl2 with 1,1,3,3‐tetramethyldisiloxane in the presence of activated carbon was found to be an effective catalyst system for the cleavage reaction of C−O bond of O−t‐Bu moieties. The present catalytic reaction offers a practical method for the deprotection of tert‐butyl esters, tert‐butyl ethers, O‐Boc, and N‐Boc derivatives under mild conditions. The addition of activated carbon in the reaction mixture was proved to be crucial for not only sustaining the catalytic activity but also trapping the palladium species after the reaction. [ABSTRACT FROM AUTHOR]