Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn2+-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.

Spatio-temporal variations of PM2.5 and O3 in China during 2013-2021: Impact factor analysis.

Fine particulate matter (PM2.5) and ozone (O3) pollution are regarded as significant secondary air pollutants. The PM2.5 in most regions in China declined, and the decreasing rate in January was lower than the annual average. However, O3 concentration showed a steady increasing trend in most regions, and the increasing rate in July was slightly higher than the annual average. In particular, the annual average PM2.5 concentration and excess rate showed an increasing trend on the northern slope of the Tianshan Mountains. Conversely, O3 concentrations had shown a consistent increasing trend, exceeding the annual average limit of 100 µg/m3. Surface pressure exhibited positive correlations with PM2.5 in winter and O3 in summer across urban agglomerations. Moreover, soil temperature at different depths explained over 30% of the variations in PM2.5 and O3 in the Chengdu-Chongqing, Beijing-Tianjin-Hebei, and Lanzhou-Xining urban agglomerations. In winter, relative humidity demonstrated a positive correlation with urban agglomerations in northeast and northwest China, regions characterized by dry climates. During the COVID-19 period, the impacts of meteorological factors and soil temperature on PM2.5 and O3 differed significantly compared to preceding and subsequent periods. Notably, during the winter of 2020, the Harbin-Changchuan urban agglomeration exhibited a notable transition, as O3 and PM2.5 concentrations shifted from a strong negative correlation to a robust positive correlation. This remarkable shift, with deviations explained up to 60%, represents a unique phenomenon worth emphasizing in the study's findings.

Advanced strategies to evade the mononuclear phagocyte system clearance of nanomaterials.

Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites of action, but their delivery efficacy is severely limited by a series of biological barriers, especially the mononuclear phagocytic system (MPS)-the first and major barrier encountered by systemically administered nanomaterials. Herein, the current strategies for evading the MPS clearance of nanomaterials are summarized. First, engineering nanomaterials methods including surface modification, cell hitchhiking, and physiological environment modulation to reduce the MPS clearance are explored. Second, MPS disabling methods including MPS blockade, suppression of macrophage phagocytosis, and macrophages depletion are examined. Last, challenges and opportunities in this field are further discussed.

Reversal of HMGA1-Mediated Immunosuppression Synergizes with Immunogenic Magnetothermodynamic for Improved Hepatocellular Carcinoma Therapy.

Magnetothermodynamic (MTD) therapy can activate antitumor immune responses by inducing potent immunogenic tumor cell death. However, tumor development is often accompanied by multifarious immunosuppressive mechanisms that can counter the efficacy of immunogenic MTD therapy. High-mobility group protein A1 (HMGA1) is overexpressed within hepatocellular carcinoma tissues and plays a crucial function in the generation of immunosuppressive effects. The reversal of HMGA1-mediated immunosuppression could enhance immunogenic tumor cell death-induced immune responses. A ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-based nanovehicle was developed, which is capable of efficiently mediating an alternating magnetic field for immunogenic tumor cell death induction, while concurrently delivering HMGA1 small interfering (si)RNA (siHMGA1) to the cytoplasm of hepatocellular carcinoma Hepa 1-6 cells for HMGA1 pathway interference. Using siHMGA1-FVIO-mediated MTD therapy, the proliferation of hepatocellular carcinoma Hepa 1-6 tumors was inhibited, and the survival of a mouse model was improved. We also demonstrated that siHMGA1-FVIO-mediated MTD achieved synergistic antitumor effects in a subcutaneous hepatocellular carcinoma Hepa 1-6 and H22 tumor model by promoting dendritic cell maturation, enhancing antigen-presenting molecule expression (both major histocompatibility complexes I and II), improving tumor-infiltrating T lymphocyte numbers, and decreasing immunosuppressive myeloid-derived suppressor cells, interleukin-10, and transforming growth factor-ß expression. The nanoparticle system outlined in this paper has the potential to target HMGA1 and, in combination with MTD-induced immunotherapy, is a promising approach for hepatocellular carcinoma treatment.

Magnetic nanomaterials-mediated neuromodulation.

Researchers have leveraged magnetic nanomaterials (MNMs) to explore neural circuits and treat neurological diseases via an approach known as MNMs-mediated neuromodulation. Here, the magneto-responsive effects of MNMs to an external magnetic field are manipulated to activate or inhibit neuronal cell activity. In this way, MNMs can serve as a nano-mediator, by converting electromagnetic energy into heat, mechanical force/torque, and an electrical field at nanoscale. These physicochemical effects can stimulate ion channels and activate precise signaling pathways involved in neuromodulation. In this review, we outline the various ion channels and MNMs that have been applied to MNMs-mediated neuromodulation. We highlight the recent advances made in this technique and its potential applications, and then discuss the current challenges and future directions of MNMs-mediated neuromodulation. Our aim is to reveal the potential of MNMs to treat neurological diseases in the clinical setting. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Design of Magnetic Nanoplatforms for Cancer Theranostics.

Cancer is the top cause of death globally. Developing smart nanomedicines that are capable of diagnosis and therapy (theranostics) in one-nanoparticle systems are highly desirable for improving cancer treatment outcomes. The magnetic nanoplatforms are the ideal system for cancer theranostics, because of their diverse physiochemical properties and biological effects. In particular, a biocompatible iron oxide nanoparticle based magnetic nanoplatform can exhibit multiple magnetic-responsive behaviors under an external magnetic field and realize the integration of diagnosis (magnetic resonance imaging, ultrasonic imaging, photoacoustic imaging, etc.) and therapy (magnetic hyperthermia, photothermal therapy, controlled drug delivery and release, etc.) in vivo. Furthermore, due to considerable variation among tumors and individual patients, it is a requirement to design iron oxide nanoplatforms by the coordination of diverse functionalities for efficient and individualized theranostics. In this article, we will present an up-to-date overview on iron oxide nanoplatforms, including both iron oxide nanomaterials and those that can respond to an externally applied magnetic field, with an emphasis on their applications in cancer theranostics.

Boosting the photothermal performance of vacancy-rich MoSe2-x nanoflowers for photoacoustic imaging guided tumor chemo-photothermal therapy.

Due to the relatively low photo-thermal conversion efficiency and poor tumor targeting capacity, phototheranostic nanoagents encounter some challenges in cancer photothermal therapy. To address this problem, in the current research we developed vacancy-rich MoSe2-x (0 ≤ x ≤ 1) nanoflowers (MNFs) with molecular 2-deoxy-D-glucose (2-DG) as the activity target, which could be used as a novel phototheranostic nanoagent in the photoacoustic imaging guided chemo-photothermal synergistic therapy. This selenium-deficient structure endows MNFs with high photothermal conversion efficiency (41.7%) due to the strong localized surface plasmon resonances. Besides, the surface linked 2-DG molecules and the flower-like morphology in the nanoagents promoted the targeting effect (active and passive), thus facilitating the efficient concentration of the nanoagents within the tumor site. Both in vitro and in vivo anti-tumor experiments have demonstrated the high synergistic efficacy promoted by MNFs and complete tumor eradication with lower administration dosages could be achieved. This rational design of nanoparticles not only provided the paradigm of high therapeutic efficacy of a chemo-photothermal protocol for precise cancer theranostics, but also expanded the scope of nanomedical applications using semiconductor-based nanoplatforms through well-defined designing of their microstructures and physiochemical properties.

Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy.

Engineering the protein corona (PC) on nanodrugs is emerging as an effective approach to improve their pharmacokinetics and therapeutic efficacy, but conventional in vitro pre-programmed methods have shown great limitation for regulation of the PC in the complex and dynamic in vivo physiological environment. Here, we demonstrate an magnetothermal regulation approach that allows us to in situ modulate the in vivo PC composition on iron oxide nanoparticles for improved cancer nanotherapy. Experimental results revealed that the relative levels of major opsonins and dysopsonins in the PC can be tuned quantitatively by means of heat induction mediated by the nanoparticles under an alternating magnetic field. When the PC was magnetically optimized in vivo, the nanoparticles exhibited prolonged circulation and enhanced tumor delivery efficiency in mice, 2.53-fold and 2.02-fold higher respectively than the control. This led to a superior thermotherapeutic efficacy of systemically delivered nanoparticles. In vivo magnetothermal regulation of the PC on nanodrugs will find wide applications in biomedicine.

[Spatio-temporal Variation Characteristics Monitored by Remotely Sensed Technique of PM2.5 Concentration and Its Influencing Factor Analysis in Sichuan Basin, China].

The spread of atmospheric pollutants in the Sichuan Basin is difficult because of its unique topography, static wind, high humidity, and other meteorological conditions. Owing to the acceleration of urbanization and industrialization, PM2.5 pollution in the region is becoming increasingly severe, and the Sichuan Basin has become one of the key areas of national air pollution prevention and control. In this study, based on the remote sensing inversion product of PM2.5 concentration, spatial autocorrelation and gray correlation analyses are used to evaluate the spatial and temporal distribution characteristics and influencing factors of PM2.5 concentration in the Sichuan Basin. The results show that PM2.5 concentration has significant spatial aggregation; the high-high aggregation types are concentrated, low-low aggregation types are more dispersed, and coniferous forest has a significantly higher inhibitory effect on the absorption of PM2.5 than the shrub, grassland, and other vegetation types. The main meteorological factors affecting PM2.5 concentration in the Sichuan Basin are wind speed and temperature; population density and economic scale are the main human-activity factors affecting PM2.5 concentration in the Sichuan Basin, and the change in the industrial structure and scale also has a certain influence on the PM2.5 concentration.

[Spatiotemporal variation and driving factors of growing season NDVI in the Tibetan Pla-teau, China.] / 青藏高原植被生长季NDVIæ—¶ç©ºå˜åŒ–ä¸Žå½±å“å› ç´ .

It is important to understand the response of vegetation to climate change in Tibetan Pla-teau (TP), an ecological barrier for China and Asia. The spatiotemporal variation of the normalized difference vegetation index (NDVI) of vegetation growing season were analyzed based on the gro-wing season NDVI retrieved from MOD09A1. The relationship between NDVI and climate factors was analyzed by combining the data of meteorological stations in TP from 2001 to 2018. The results showed that NDVI in the growing season showed a slow upward trend during the study period. There was substantial interannual variation of NDVI in different climate regions. The fluctuation magnitude of NDVI value was plateau humid climate region>semi-humid climate region>semi-arid climate region>arid climate region. The proportion of area with increasing and decreasing NDVI in humid climate region, semi-humid climate region, arid climate region, semi-arid climate region on TP were 1.4% and 1.9%, 4.9% and 1.5%, 16.4% and 0.8%, 7.0% and 2.0%, respectively. The areas of increasing NDVI in arid and semi-arid climate region was significantly larger than humid and semi-humid region. Temperature was the leading factor affecting the change of NDVI in humid and semi-humid region. The impact of precipitation on NDVI was significantly stronger than that of other climate factors in arid region. The impact of air temperature in growing season on NDVI was stronger than that of precipitation and relative humidity.

Proton-driven transformable nanovaccine for cancer immunotherapy.

Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer-peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.

Iron nanoparticles augmented chemodynamic effect by alternative magnetic field for wound disinfection and healing.

Utilizing the iron-carrying nanomaterials for Fenton chemistry mediation to catalyze decomposition of hydrogen peroxide and generate toxic hydroxyl radical (OH) has drawn much attention in antimicrobial therapy field. However, these nanomaterials are usually with unsatisfactory catalytic efficacy and lack of the capacity to modulate the catalytic activity, which may give the bacteria opportunity in developing resistance against the antibacterial treatment. Herein, we systematically investigated the influence of alternating magnetic field (AMF) on the catalytic activity and antibacterial efficiency of the amorphous iron nanoparticles (AIronNPs). With rapidly ionized and the AMF augmented chemodynamic effect, the AIronNPs can convert low concentration of H2O2 into more OH, the possible mechanism might be attributed to the accelerated ferrous iron ions releasing with AMF exposure. As a proof of concept, the AIronNPs and AMF synergetic antibacterial system have shown excellent broad-spectrum antimicrobial properties, 91.89% antibacterial efficiency is shown toward Escherichia coli and 92.65% toward Staphylococcus aureus. It also facilitated the formation of granulation tissue and accelerated wound healing on in vivo infected model, whereas AIronNPs alone have limited effect. We believe this work will broaden the thoughts for spatiotemporally manipulating the catalytic activity of nanomaterials and advance the development of magnetic nano-antibiotics in the antibacterial field.

Graphene Oxide-Grafted Magnetic Nanorings Mediated Magnetothermodynamic Therapy Favoring Reactive Oxygen Species-Related Immune Response for Enhanced Antitumor Efficacy.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

Ellipsoidal magnetite nanoparticles: a new member of the magnetic-vortex nanoparticles family for efficient magnetic hyperthermia.

The development of magnetic iron oxide nanoparticles with novel topological magnetic domain structures, such as the vortex-domain structure, is a promising strategy for improving the application performance of conventional superparamagnetic iron oxides while maintaining their good biocompatibility. Here, we fabricated a new kind of magnetic-vortex nanoparticles, i.e., ellipsoidal magnetite nanoparticles (EMPs), for cancer magnetic hyperthermia. The magnetization configurations and switching behaviours of the EMPs were analyzed by analytical simulations and Lorentz TEM, demonstrating the magnetic vortex structures of both single and coupled EMPs. The EMP treatment of 4T1 cells exposed to an alternating magnetic field (AMF) induced a significant decrease in the cell viability by ∼51.5%, which indicated a much higher cytotoxic effect in comparison with commercial superparamagnetic iron oxides (Resovist, ∼12.0%). In addition, the in vivo high efficacy of 4T1 breast tumor inhibition was also achieved by using EMP-mediated magnetic hyperthermia. Our results not only provide a new type of magnetic-vortex nanoparticles for efficient hyperthermia but also enrich the family of magnetic iron oxide nanoparticles for various biomedical applications.

Vegetation dynamic analysis based on multisource remote sensing data in the east margin of the Qinghai-Tibet Plateau, China.

This study focuses on the vegetation dynamic caused by global environmental change in the eastern margin of the Qinghai-Tibet Plateau (EMQTP). The Qinghai-Tibet Plateau (QTP) is one of the most sensitive areas responding to global environmental change, particularly global climate change, and has been recognized as a hotspot for coupled studies on changes in global terrestrial ecosystems and global climates. An important component of terrestrial ecosystems, vegetation dynamic has become a key issue in global environmental change, and numerous case studies have been conducted on vegetation dynamic trends using multi-source data and multi-scale methods across different study periods. The EMQTP is regarded as a transitional area located between the QTP and the Sichuan basin, and has special geographical and climatic conditions. Although this area is ecologically fragile and sensitive to climate change, few studies about vegetation dynamics have been carried out in this area. Thus, in this study, we used long-term series datasets of GIMMS 3g NDVI and VGT/PROBA-V NDVI to analyze the vegetation dynamics and phenological changes from 1982 to 2018. Validation was performed based on Landsat NDVI and Vegetation Index & Phenology (VIP) data. The results reveal that the year 1998 was a vital turning point in the start of growing season (SGS) in vegetation ecosystems. Before this turning point, the SGS had an average slope of 9.2 days/decade, and after, the average slope was 3.9 days/decade. The length of growing season (LGS) was slightly prolonged between 1982 to 2015. Additionally, the largest national alpine wetland grassland experienced significant vegetation degradation; in autumn, the degraded area accounted for 63.4%. Vegetation degradation had also appeared in the arid valleys of the Yalong River and the Jinsha River. Through validation analysis, we found that the main causes of vegetation degradation are the natural degradation of wetland grassland and human activities, specifically agricultural development and residential area expansion.

Dynamic Changes of NDVI in the Growing Season of the Tibetan Plateau During the Past 17 Years and Its Response to Climate Change.

The fragile alpine vegetation in the Tibetan Plateau (TP) is very sensitive to environmental changes, making TP one of the hotspots for studying the response of vegetation to climate change. Existing studies lack detailed description of the response of vegetation to different climatic factors using the method of multiple nested time series analysis and the method of grey correlation analysis. In this paper, based on the Normalized Difference Vegetation Index (NDVI) of TP in the growing season calculated from the MOD09A1 data product of Moderate-resolution Imaging Spectroradiometer (MODIS), the method of multiple nested time series analysis is adopted to study the variation trends of NDVI in recent 17 years, and the lag time of NDVI to climate change is analyzed using the method of Grey Relational Analysis (GRA). Finally, the characteristics of temporal and spatial differences of NDVI to different climate factors are summarized. The results indicate that: (1) the spatial distribution of NDVI values in the growing season shows a trend of decreasing from east to west, and from north to south, with a change rate of -0.13/10° E and -0.30/10° N, respectively. (2) From 2001 to 2017, the NDVI in the TP shows a slight trend of increase, with a growth rate of 0.01/10a. (3) The lag time of NDVI to air temperature is not obvious, while the NDVI response lags behind cumulative precipitation by zero to one month, relative humidity by two months, and sunshine duration by three months. (4) The effects of different climatic factors on NDVI are significantly different with the increase of the study period.

Ferrimagnetic Vortex Nanoring-Mediated Mild Magnetic Hyperthermia Imparts Potent Immunological Effect for Treating Cancer Metastasis.

Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8+ cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8+ cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.

Nonmagnetic Hypertonic Saline-Based Implant for Breast Cancer Postsurgical Recurrence Prevention by Magnetic Field/pH-Driven Thermochemotherapy.

Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.

Carbon-dot-supported atomically dispersed gold as a mitochondrial oxidative stress amplifier for cancer treatment.

Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications.

Injectable and self-healing polysaccharide-based hydrogel for pH-responsive drug release.

Injectable hydrogels with self-healing and pH-responsive property are appealing for biomedical applications. Herein, we developed a facile and green method to prepare a multifunctional polysaccharide-based hydrogel as a new carrier of drug. The hydrogels were prepared by forming reversible chemical bond between carboxyethyl-modified chitosan (CEC) and aldehyde modified hyaluronic acid (A-HA). The morphology and rheological property of the hydrogels with different solid content were systematically characterized. Owing to the dynamic equilibrium of the Schiff base bonds between amine groups on CEC and aldehyde groups on A-HA, the rapid self-healing performance of hydrogels was confirmed through qualitative and quantitative methods without any external stimulus. The pH-responsive behaviour was demonstrated by equilibrium swelling and in vitro Doxorubicin (Dox) release in PBS medium with various pH. In acidic condition, Dox can be release more rapidly compared with weak alkaline medium. Furthermore, the kill effect of Dox released from hydrogels for cancer cells was investigated. In vitro degradation and cytotoxicity examinations showed that the hydrogel is biodegradable and biocompatible. Therefore, such polysaccharide-based injectable self-healing and pH-responsive hydrogel is a promising candidate as drug delivery carrier.