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The influence of metabolic syndrome (MetS) on long-term prognosis of patients with myocardial infarction (MI), the most severe type of coronary artery disease, remains not fully determined. This systematic review and meta-analysis were conducted to investigate the association between MetS and long-term clinical outcomes of patients with MI. A systematic search of Medline, Web of Science, and Embase databases from inception to June 25, 2023, was conducted to obtain eligible studies. Only studies with follow-up duration for at least one year were considered. A random-effects model was utilized to pool the results, accounting for heterogeneity. Ten observational studies were included, which included 33 197 patients with MI. Among them, 17 244 (51.9%) were with MetS at baseline. During a follow-up duration of 12 to 48 months (mean: 22.5 months), patients with MetS were associated with higher incidence of major adverse cardiovascular events [risk ratio (RR): 1.35. 95% confidence interval (CI): 1.19 to 1.54, p<0.001; I2=64%] and all-cause deaths (RR: 1.34, 95% CI: 1.18 to 1.52, p<0.001; I2=23%), as compared to those without MetS at baseline. Subgroup analyses showed that the results were not significantly affected by study characteristics such as study country, design, type of MI, mean age of the patients, treatment with percutaneous coronary intervention, follow-up durations, or study quality scores (p for subgroup difference all>0.05). In patients with MI, MetS may be a risk factor of poor long-term prognosis. [ABSTRACT FROM AUTHOR]

We propose a method to engineer the light matter interaction while initializing a qubit present of physical constraints utilizing the inverse engineering. Combining the multiple degrees of freedom in the pulse parameters with the perturbation theory, we develop pulses to initialize the qubit within a tightly packed frequency interval to an arbitrary superposition state with high fidelity. Importantly, the initialization induces low off-resonant excitations to the neighboring qubits, and it is robust against the spatial inhomogeneity in the laser intensity. We apply the method to the ensemble rare-earth ions system, and simulations show that the initialization is more robust against the variations in laser intensity than the previous pulses, and reduces the time that ions spend in the intermediate excited state by a factor of 17. The method is applicable to any systems addressed in frequency such as nitrogen-vacancy centers, superconducting qubits, quantum dots, and molecular qubit systems. [ABSTRACT FROM AUTHOR]

Enrichment of selenium (Se) by seaweed is of great significance for mariculture. In this study, the green alga Ulva fasciata was cultured with a selenite (NaSeO) concentration from 0 to 1,250 mg L. Se accumulation in the algal biomass was linearly related to NaSeO concentration in the culture medium. Lower Se concentrations (≤750 mg L) increased the activities of guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) and the content of photosynthetic pigments, and as well induced lipid peroxidation (LPO) and intracellular reactive oxygen species (ROS) levels. Meanwhile, the cell growth rate and concentrations of organic Se increased. In contrast, these changes were the opposite in U. fasciata exposed to Se concentrations higher than 750 mg L. In all cases, Se- Ulva was able to remove inorganic nutrients effectively. Therefore, U. fasciata is tolerant to Se, and Se- Ulva has potential as a source of antioxidative food and an effective control of eutrophication. [ABSTRACT FROM AUTHOR]

Autophagy could play suppressing role in cancer therapy by facilitating release of tumor antigens from dying cells and inducing immunogenic cell death (ICD). Therefore, discovery and rational design of more effective inducers of cytotoxic autophagy is expected to develop new strategies for finding innovative drugs for precise and successful cancer treatment. Herein, we develop MoO3‐x nanowires (MoO3‐x NWs) with high oxygen vacancy and strong photothermal responsivity to ablate tumors through hyperthermia, thus promote the induction of cytotoxic autophagy and severe ICD. As expected, the combination of MoO3‐x NWs and photothermal therapy (PTT) effectively induces autophagy to promote the release of tumor antigens from the ablated cells, and induces the maturation and antigen presentation of dendritic cells (DCs), subsequently activates cytotoxic T lymphocytes (CTLs)‐mediated adaptive immunity. Furthermore, the combination treatment of MoO3‐x NWs with immune checkpoint blockade of PD‐1 could promote the tumor‐associated macrophages (TAMs) polarization into tumor‐killing M1 macrophages, inhibit infiltration of Treg cells at tumor sites, and alleviate immunosuppression in the tumor microenvironment, finally intensify the anti‐tumor activity in vivo. This study provides a strategy and preliminary elucidation of the mechanism of using MoO3‐x nanowires with high oxygen vacancy to induce autophagy and thus enhance photothermal immunotherapy. [ABSTRACT FROM AUTHOR]

Autophagy could play suppressing role in cancer therapy by facilitating release of tumor antigens from dying cells and inducing immunogenic cell death (ICD). Therefore, discovery and rational design of more effective inducers of cytotoxic autophagy is expected to develop new strategies for finding innovative drugs for precise and successful cancer treatment. Herein, we develop MoO3‐x nanowires (MoO3‐x NWs) with high oxygen vacancy and strong photothermal responsivity to ablate tumors through hyperthermia, thus promote the induction of cytotoxic autophagy and severe ICD. As expected, the combination of MoO3‐x NWs and photothermal therapy (PTT) effectively induces autophagy to promote the release of tumor antigens from the ablated cells, and induces the maturation and antigen presentation of dendritic cells (DCs), subsequently activates cytotoxic T lymphocytes (CTLs)‐mediated adaptive immunity. Furthermore, the combination treatment of MoO3‐x NWs with immune checkpoint blockade of PD‐1 could promote the tumor‐associated macrophages (TAMs) polarization into tumor‐killing M1 macrophages, inhibit infiltration of Treg cells at tumor sites, and alleviate immunosuppression in the tumor microenvironment, finally intensify the anti‐tumor activity in vivo. This study provides a strategy and preliminary elucidation of the mechanism of using MoO3‐x nanowires with high oxygen vacancy to induce autophagy and thus enhance photothermal immunotherapy. [ABSTRACT FROM AUTHOR]

• Overview of the transition metal complexes as photosensitizers. • Integration of metal complexes with biomolecules for targeted antitumor application. • The future perspectives for metal-based PSs are outlined. Light, oxygen and photosensitizers (PSs) are the three separate elements that have been applied in combination in the phototherapy of cancers in the past decades. Currently, platinum (Pt)-based drugs still account for approximately 50% of traditional chemotherapies used in the clinic. Transition metal complexes with unique and versatile photochemical and photophysical properties have appeared as promising systems for both photodynamic therapy and photoactivated chemotherapy. The highly potent photobiological activity based on energy transfer and electron transfer processes takes advantage of these properties. In this perspective article, we discuss the development of transition metal complexes (TMCs) with meaningful designs for the diagnosis and therapy of malignant tumors, including octahedral Ru(II) (ruthenium), Pt(IV) and Rh(III) (rhodium) PSs and in the early stages of Ir(III) (iridium) and Os(II) (osmium) complexes. The combination of organometallics with other active targeting moieties, such as antibodies, peptides, and aptamers, resulting in increased selectivity and reduced side-effects, will then be discussed. The challenges and future perspectives in this field will also be discussed. This review not only provides useful information for the future design of chemically innovative TMC-based anticancer drug candidates with clear mechanisms of action and drug targets, but also sheds light into the discovery of metal-based PSs to improve cancer treatment. [ABSTRACT FROM AUTHOR]

Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon within methacrylate gelatin (O2‐PSSG). The resultant construct orchestrates the modulation of the bone‐defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium‐containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O2‐PSSG rapidly releases selenocystine ([Sec]2) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β‐catenin pathways and promotes the differentiation of BMSCs. Consequently, O2‐PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US‐responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) poses a significant challenge in local treatment, primarily attributed to its intricate tumor immune microenvironment. The immunosuppression of natural killer (NK) cells within the microenvironment, exacerbated by selenium (Se) deficiency, constitutes a pivotal treatment bottleneck. Building upon prior investigations, this study delves into the impact and mechanisms of functionalized lentinan selenium nanoparticles (LET‐SeNPs) on NK cells in MPE, presenting a novel local treatment strategy for lung adenocarcinoma with malignant pleural effusion (MPE‐LA). The synergistic application of LET‐SeNPs serves to replenish Se levels in MPE, modulate NK cells, augment their quantity, restore and enhance their functionality. Additionally, LET‐SeNPs facilitate NK cells activation through the TrxR1‐IL18RAP‐pSTAT3 pathway, resulting in effective lung cancer cell eradication and reduced pleural effusion production. Furthermore, pre‐stimulation of NK cells by LET‐SeNPs, combined with CAR‐NK cell therapy, harnesses the innate immune system, exhibiting a potent anti‐tumor effect. This research introduces a compelling strategy to advance the clinical implementation of targeted nanomaterials or lead compounds with explicit targets and mechanisms, thereby enhancing NK cell therapy for comprehensive diagnosis and treatment of MPE. [ABSTRACT FROM AUTHOR]

Radiotherapy, as one of the most common strategies for clinical cancer treatment, suffers from failure due to the hypoxia, inflammation, and radiosensitivity difference of malignant tumors, side effects, and radioresistance. Heterojunction‐based radiosensitizers attract great attention to the lower excitation energy and remarkable catalytic activity as compared to typical transition metal radiosensitizers. However, the bio‐application of heterojunction radiosensitizers is in its infancy due to the challenges in structure engineering, rational energy band alignment, and ideal photogenerated carrier migration. Herein, a bimetallic metal‐organic framework (MOF)‐based heterojunction radiosensitizer is reasonably designed to enhance the radiodynamic therapeutic efficiency of Ru complex, and to activate natural killer (NK) cell‐mediated innate immune responses for promoted tumor immunotherapy. This study not only designs a novel bimetallic MOF‐based heterojunction structure but also elucidates the underlying action mechanisms in inhibiting cancer proliferation, which sheds light on the practicable design of radiosensitizers and the tumor combination treatment. [ABSTRACT FROM AUTHOR]

Inactivated virus vaccines with whole antigen spectra and good safety are the commonly used modality for preventing infections. However, the poor immunogenicity greatly limits its clinical applications. Herein, by taking advantages of the crucial roles of Se in the functions of immune cells and its biomineralization property, it successfully in‐situ synthesized Se nanoadjuvant on inactivated viruses such as porcine epidemic diarrhea virus (PEDV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a facile method, which is universal to construct other inactivated virus vaccines. The nanovaccine can highly effectively enhance the uptake of PEDV/PRV/PRRSV into dendritic cells (DCs) and activate DCs via triggering TLR4 signaling pathways and regulating selenoproteins expressions. Furthermore, it exhibited better activities in triggering macrophages and natural killer cells‐mediated innate immunity and T cells‐mediated cellular immunity compared to PEDV and the commercial inactivated PEDV vaccine on both mice and swine models. This study provides a universal Se nanoadjuvant for developing inactivated viruses‐based nanovaccines for preventing virus infections. [ABSTRACT FROM AUTHOR]

Activation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu2‐xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu2‐xSe) as a copper‐carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis‐driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid‐triggered charge‐switching ability. Next step, the exposed Cu2‐xSe is oxidized and releases divalent copper by high‐level oxide. Then, the abundant copper induces more dihydrolipoamide S‐acetyltransferase oligomerization to down‐regulate FDX1 and tricarboxylic acid cycle‐related proteins, which leads to inhibiting aerobic respiration. Cuproptosis‐induced mitochondrial damage further improves thermotherapy by up‐regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu2‐xSe with sequentially triggered copper‐release, efficient cuproptosis, and appropriate photothermal is a self‐enhanced nanoplatform for cuproptosis‐driven enhancement of thermotherapy. [ABSTRACT FROM AUTHOR]

Gracilaria is the second most productive genus of mariculture seaweeds after Laminaria in China. It is important to increase its economic value. The purpose of this study was to document the accumulation and biotransformation of selenium in Gracilaria lemaneiformis. The seaweed was cultured for 12 days in medium containing from 0 to 2000 mg L−1 selenite. At concentrations lower than 750 mg L−1, seaweed growth was promoted and the amount of chlorophyll a decreased. The organic Se content in the seaweed was over 80% in all groups and was as much as 400 μg g−1 of dry weight. Se enrichment induced a decrease in the activities of superoxide dismutase in the seaweed cells. These results suggest that G. lemaneiformis is tolerant to Se and prevents phytotoxicity by altering various metabolic processes. Furthermore, this seaweed exhibits great potential to transform inorganic Se into the organic form and therefore could be a safe candidate for the production of Se-enriched functional food. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering. [ABSTRACT FROM AUTHOR]

Developing radiosensitizers based on the characteristics of the tumor microenvironment can improve the effectiveness and overcome the bottleneck of cervical cancer radiotherapy. Herein, an in situ synthesis strategy is demonstrated by using a highly bioactive zeolitic imidazolate framework to cap Mn3O4 and folic acid as targeting molecules (FA‐Mn3O4@ZIF‐8) to achieve enhanced radiosensitization against cervical cancer. As expected, the ZIF‐8 cap on the surface of Mn3O4 responds more effectively to X‐rays. Meanwhile, by facilitating the presence of oxygen vacancies and valence transition of manganese on the surface of Mn3O4, the ZIF‐8 cap on Mn3O4 can increase the catalytic capacity for hydrogen peroxide (H2O2) and glutathione as well as produce more singlet oxygen under X‐ray, alleviate hypoxia within the tumor microenvironment, and increase reactive oxygen species production. Moreover, FA‐Mn3O4@ZIF‐8 shows excellent radiotherapy‐sensitizing properties in vitro and in vivo by promoting DNA damage and apoptosis. Collectively, this study suggests that designing and construction of X‐ray responsive nanoradiosensitizers could be a good way for future clinical radiotherapy of malignant cervical cancer. [ABSTRACT FROM AUTHOR]

The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development. [ABSTRACT FROM AUTHOR]

Low persistence, metabolic dysfunction in microenvironment, and tumor-derived immunosuppression of Natural killer (NK) cells in patients are greatly limited the successful clinical application of NK cell-based cancer immunotherapy. Interestingly, herein that human serum albumin-encapsulated black phosphorus quantum dots (BPQDs@HSA) can effectively augment antitumor efficacy of clinical patients-derived NK cell immunotherapy is found. As the donor of phosphate group, BPQDs@HSA binds with the protein of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1A) and activates the downstream PI3K-Akt and mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. And multiomics analysis is therefore conducted to reveal the underlying immunoregulation mechanisms, and that BPQDs@HSA can interact with the Toll-like receptor (TLR) on the NK cell surface and increase the expression level of mTOR, and thus activate downstream NF-KB signalling pathways to regulate cytokine secretion and enhance immune tumoricidal is found. BPQDs@HSA can also enhance immune surveillance, relieve immune suppression, and inhibit tumor immune escape. Collectively, this study not only demonstrates a successful strategy for nanomedicine-potentiated immune-cancer therapy, but also sheds light on the understanding of interface between nanomedicine and immune cells activation. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H2O2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. Results: Therefore, to further improve the efficiency of radiotherapy, a core–shell nanocomposite CeO2–MnO2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO2–MnO2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO2 reacts with GSH and H2O2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO2–MnO2, due to its high atomic number oxide CeO2, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. Conclusion: In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is among the most common malignant tumors of the genitourinary system worldwide. In recent years, the rate of BC incidence has increased, and the recurrence rate is high, resulting in poor quality of life for patients. Therefore, how to develop an effective method to achieve synchronous precise diagnoses and BC therapies is a difficult problem to solve clinically. Previous reports usually focus on the role of nanomaterials as drug delivery carriers, while a summary of the functional design and application of nanomaterials is lacking. Summarizing the application of functional nanomaterials in high‐sensitivity diagnosis and multimodality therapy of BC is urgently needed. This review summarizes the application of nanotechnology in BC diagnosis, including the application of nanotechnology in the sensoring of BC biomarkers and their role in monitoring BC. In addition, conventional and combination therapies strategy in potential BC therapy are analyzed. Moreover, different kinds of nanomaterials in BC multimodal therapy according to pathological features of BC are also outlined. The goal of this review is to present an overview of the application of nanomaterials in the theranostics of BC to provide guidance for the application of functional nanomaterials to precisely diagnose and treat BC. [ABSTRACT FROM AUTHOR]

Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the chemical conjugation of imaging agents to the surface of nanoparticles, which may impede the later clinical translation. In this study, we developed a label-free strategy in which lentinan-functionalized SeNPs (LNT-SeNPs) are detected using MRI by the hydroxyl protons carried on LNT molecules. The in vitro phantom study showed that LNT and LNT-SeNPs have a strong CEST signal at 1.0 ppm apart from the water resonance, suggesting an in vivo detectability in the µM concentration range. Demonstrated on CT26 colon tumor cells, LNT-SeNPs exert a strong anticancer effect (IC50 = 4.8 μM), prominently attributed to the ability to generate intracellular reactive oxygen species. However, when testing in a mouse model of CT26 tumors, administration of LNT-SeNPs alone was found unable to deliver sufficient drugs to the tumor, leading to poor treatment responses. To improve the drug delivery, we co-injected LNT-SeNPs and TNF-α, a previously reported drug that could effectively damage the endothelial cells in the tumor vasculature, thereby increasing drug delivery to the tumor. Our results revealed a 75% increase in the intratumoral CEST MRI signal, indicating a markedly increased delivery efficiency of LNT-SeNPs when combined with TNF-α. The combination therapy also resulted in a significantly enhanced treatment outcome, as revealed by the tumor growth study. Taken together, our study demonstrates the first label-free, SeNP-based theranostic system, in which LNT was used for both functional surface coating and CEST MRI signal generating. Such a theranostic LNT-SeNP system is advantageous because it requires chemical labeling and, therefore, has high biocompatibility and low translatable barriers. [ABSTRACT FROM AUTHOR]

Background: Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility. Results: Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo. Conclusion: In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects. [ABSTRACT FROM AUTHOR]

6061 aluminum alloy is one of the light metal materials, which has the advantages of good elasticity and lightweight. However, aluminum alloy is susceptible to corrosion in industrial applications. Therefore, in this paper, we successfully prepared an organic lauric acid film on the surface of aluminum alloy by electrodeposition. The film was characterized by SEM, EDS, WCA, XPS, EIS, FT‐IR, and neutral salt spray test. According to the results of the EIS test, impedance value has increased by two orders of magnitude compared to the substrate, and corrosion current density reached 8.51 × 10−7 A/cm2. The salt spray test was conducted for 192 h before the corrosion point appeared, indicating that the film have better anticorrosion ion permeability. Calculated chemical results show that COOH of lauric acid is the dominant reaction group and the carboxyl group is near the aluminum alloy surface for the reaction equilibrium state, which provide a theoretical basis for the study of the film. [ABSTRACT FROM AUTHOR]

Background: As Traditional Chinese Medicine (TCM) drugs, Huangqi and Danshen are always applied in combination for spinal cord injury (SCI) treatment based on the compatibility theory of TCM. Astragalus Polysaccharidesis (APS) and Tanshinone IIA (TSIIA) are the main active ingredients of Huangqi and Danshen, and they both possess neuroprotective effects through antioxidant activities. However, low solubility and poor bioavailability have greatly limited their application. In recent years, selenium nanoparticles (SeNPs) have drawn enormous attention as potential delivery carrier for antioxidant drugs. Results: In this study, TCM active ingredients-based SeNPs surface decorated with APS and loaded with TSIIA (TSIIA@SeNPs-APS) were successfully synthesized under the guidance of the compatibility theory of TCM. Such design improved the bioavailability of APS and TSIIA with the benefits of high stability, efficient delivery and highly therapeutic efficacy for SCI treatment illustrated by an improvement of the antioxidant protective effects of APS and TSIIA. The in vivo experiments indicated that TSIIA@SeNPs-APS displayed high efficiency of cellular uptake and long retention time in PC12 cells. Furthermore, TSIIA@SeNPs-APS had a satisfactory protective effect against oxidative stress-induced cytotoxicity in PC12 cells by inhibiting excessive reactive oxygen species (ROS) production, so as to alleviate mitochondrial dysfunction to reduce cell apoptosis and S phase cell cycle arrest, and finally promote cell survival. The in vivo experiments indicated that TSIIA@SeNPs-APS can protect spinal cord neurons of SCI rats by enhancing GSH-Px activity and decreasing MDA content, which was possibly via the metabolism of TSIIA@SeNPs-APS to SeCys2 and regulating antioxidant selenoproteins to resist oxidative stress-induced damage. Conclusions: TSIIA@SeNPs-APS exhibited promising therapeutic effects in the anti-oxidation therapy of SCI, which paved the way for developing the synergistic effect of TCM active ingredients by nanotechnology to improve the efficacy as well as establishing novel treatments for oxidative stress-related diseases associated with Se metabolism and selenoproteins regulation. [ABSTRACT FROM AUTHOR]

Molecular phototheranostics as an emerging field of modern precision medicine has recently attracted increasing research attention owing to non‐invasiveness, high precision, and controllable nature of light. In this work, we reported promising gadolinium (Gd3+) porphyrinoids as phototheranostic agents for magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The synthesized Gd‐1‐4‐Glu featured with meso‐glycosylation and β‐lactonization to endow good biocompatibility and improved photophysical properties. In particular, β‐lactonization of glycosylated Gd3+ porphyrinoids substantially red‐shifted Q band absorption to near‐infrared (NIR) region and boosted generation of reactive oxygen species including 1O2, and some radical species that engaged in both type II and type I PDT pathways. In addition, the number and regioisomerism of β‐oxazolone moieties was observed to play an essential role in improving longitude relaxivity (r1) of Gd‐1‐4‐Glu of up to 4.3±0.2 mM−1s−1 by affecting environmental water exchange. Taking Gd‐4‐Glu as a promising complex, we further achieved real‐time T1‐weighted MRI and PDT on HeLa tumour mice in vivo, revealing the appealing potential of Gd3+ porphyrinoids in phototheranostics. [ABSTRACT FROM AUTHOR]

Vaccination with subunit nanovaccines is a promising strategy to combat virus infection and tumor development. However, immunogenicity of present nanovaccines is still unsatisfied for clinical translation. Here, we developed a nanovaccine loading a STING agonist, 2′3′-cGAMP and, a model subunit antigen, OVA, by using a well-defined self-degradable poly(β-amino ester)s to treat B16F10-OVA melanoma tumors. The polymer underwent slow hydrolysis at pH 5.5 but self-degraded induced by the amino groups along the polyester chain at pH > 6.5. It is shown that the self-degradation products facilitated the release of 2′3′-cGAMP and OVA from early endolysome to the cytosol, where the two components strongly activated CD8+ T lymphocytes (CTLs) and significantly enhanced Ifn1, TNF, Cxcl9, and Cxcl10 expression. In turn, the tumor microenvironment was remolded from cold to hot. Moreover, the nanovaccine could be quickly drained to sentinel lymph nodes after intratumoral injection. The nanovaccine with strong immunogenicity also could reduce the side effects of systemic inflammatory reaction caused by molecular 2′3′-cGAMP. The tumor progression of animals was inhibited, and their survival rates increased significantly. Thus, the multifunctional biodegradable material provided a new delivery system for a cancer vaccine to translate to clinics. [Display omitted] [ABSTRACT FROM AUTHOR]

Radioresistance and limitation of irradiative dosage usually lead to failure in depletion of hypoxic tumors. Herein we developed multifunctional mesoporous silica nanoparticles (MSNs) as a carrier of a novel anticancer selenoamino acid (selenocystine, SeC), to achieve synergistic chemo-/radiotherapy. This multifunctional nanosystem effectively sensitizes cancer cells to X-ray radiotherapy. Conjugation of TAT cell penetrating peptide and transferrin to the surface of MSNs significantly enhances its internalization in cancer cells through receptor-mediated endocytosis. SeC@MSNs-Tf/TAT significantly enhanced X-ray-induced growth inhibition in cervical cancer cells by induction of apoptosis, mainly through death receptor-mediated extrinsic apoptotic pathway. Upon radiation, SeC@MSNs-Tf/TAT promoted intracellular ROS overproduction, which induced apoptotic cell death by affecting p53, AKT and MAPKs pathways. Furthermore, SeC@MSNs-Tf/TAT also significantly inhibited HeLa tumor growth in nude mice model through suppression of cell proliferation and induction of apoptosis. In vivo toxicity of the SeC@MSNs-Tf/TAT nanoparticles was investigated using the mouse model. The results of histological analysis revealed that, the nanoparticles did not show any obvious damage to these major organs under the experimental conditions, including heart, liver, spleen, lung and kidney. Taken together, this study demonstrates an effective and safe strategy for cancer-targeted chemo-/radiotherapy of human cancers. [ABSTRACT FROM AUTHOR]

We report here a simple but efficient "ship-in-a-bottle" synthetic strategy for increasing the stability and luminescence performance of LOPs by embedding them into mesoporous silica nanoparticles (MSNs). Three types of hybrid materials, i.e. Eu8L12@MSNs, Eu8L12@MSNs-NH2 and Eu8L12@MSNs-biotin, have been prepared and characterized by FT-IR, TGA, SEM and TEM. Photo-optical measurements confirmed that the photoluminescence quantum yields in water have been greatly improved from 5.50% for pristine Eu8L12 to 44.04% for Eu8L12@MSNs-biotin, along with fast disassembly for the former and the optical performance has been maintained for the latter under acidic conditions (pH = 4). Moreover, compared to Eu8L12, Eu8L12@MSNs and Eu8L12@MSNs-NH2, the biotin-modified hybrid material Eu8L12@MSNs-biotin has exhibited much enhanced fluorescence-imaging ability toward the MDA-MB-231 human breast cancer cells, with significantly reduced dosage of the complex. Our work provides a useful strategy for the functionalization of multinuclear lanthanide organic assemblies toward their biosocial applications. [ABSTRACT FROM AUTHOR]

Designing metal complexes to target the vulnerable redox balance in cancer cells is a promising strategy to realize successful cancer therapy. The synthesized stable nitridomanganese(V) complex MnV(N) (salen) not only reacts with GSH to achieve in situ Mn(V)–Mn(III) transformation to down-regulate the antioxidant system, but also catalyzes H2O2 to higher oxidation capacity ROS to up-regulate the intracellular oxidative level, finally resulting in cancer cell death. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. Methods: A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. Results: The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. Conclusions: Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC. [ABSTRACT FROM AUTHOR]

Herein we demonstrate a new strategy by introducing Se atom with strong polarization effects to obtain highly bioactive organoselenium with electrophilic center. Organoselenium interact with Cys16 and Thr18 of PDGFB in malignant osteosarcoma MG63 cells through non-covalent bond, which further block the activation of intracellular AKT/JNK and downstream signaling pathways to promote cancer cells apoptosis. [Display omitted] • Organic selenium with high bioactivity electrophilic center was synthesized. • Org-Se can target PDGFB protein in MG63 cells and promote apoptosis. • Org-Se combined with radiotherapy can promote apoptosis of MG63 cells. Growth factor-like proteins play an important role in promoting oncogenesis. Therefore, designing specific inhibitors of such targets would facilitate the development of targeted drugs with low toxicity. However, low affinity and poor specificity between drugs and target proteins always affect the selectivity and action efficacy. Herein we demonstrates a new strategy by introducing selenium (Se) atom with strong polarization effects to obtain highly bioactive organoselenium with electrophilic center. The results of target-capturing analysis reveals that organoselenium interact with Cys16 and Thr18 of the platelet-derived growth factor B (PDGFB) protein in malignant osteosarcoma MG63 cells through non-covalent bond, thus inhibiting the expression and activity of PDGFB, which further block the activation of intracellular protein kinase B/c-Jun N-terminal kinases (AKT/JNK) and downstream signaling pathways to promote cancer cells apoptosis. Taken together, we have developed a novel strategy by introducing Se-based electrophilic centers for the development of targeted therapeutic agents for malignant tumors. [ABSTRACT FROM AUTHOR]

In the article "Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair," Hongmei Liu, Tianfeng Chen, and their colleagues introduce an innovative hydrogel platform that can be controlled by ultrasound to promote the repair of bone injuries. The hydrogel contains a thin-shell silicon incorporated with selene and oxygen, which is released under ultrasound control. This process helps to remodel the microenvironment of bone defects by addressing hypoxia and high levels of reactive oxygen species. The researchers believe that this hydrogel platform shows promising potential for promoting bone regeneration. [Extracted from the article]

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment. [ABSTRACT FROM AUTHOR]

Gas therapy (GT) has attracted increasing attention in recent years as a new cancer treatment method with favorable therapeutic efficacy and reduced side effects. Several gas molecules, such as nitric oxide (NO), carbon monoxide (CO), hydrogen (H2), hydrogen sulfide (H2S) and sulfur dioxide (SO2), have been employed to treat cancers by directly killing tumor cells, enhancing drug accumulation in tumors or sensitizing tumor cells to chemotherapy, photodynamic therapy or radiotherapy. Despite the great progress of gas therapy, most gas molecules are prone to nonspecific distribution when administered systemically, resulting in strong toxicity to normal tissues. Therefore, how to deliver and release gas molecules to targeted tissues on demand is the main issue to be considered before clinical applications of gas therapy. As a specific and noninvasive stimulus with deep penetration, near-infrared (NIR) light has been widely used to trigger the cleavage and release of gas from nano-prodrugs via photothermal or photodynamic effects, achieving the on-demand release of gas molecules with high controllability. In this review, we will summarize the recent progress in cancer gas therapy triggered by NIR light. Furthermore, the prospects and challenges in this field are presented, with the hope for ongoing development. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management. [ABSTRACT FROM AUTHOR]

Background: The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent. Results: Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo. Conclusions: Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound (HIFU) has been widely used in clinical treatment of cervical cancer for its non-invasiveness and sharp treatment margins with very low complication rates. However, how to intensify the therapeutic efficacy of HIFU by specifically focusing the ultrasound energy on targeting pathological tissues is still a bottleneck for it to realize successful cancer ablation. Herein, a multifunctional organic-inorganic hybrid nanovesicles, by coating ultrathin silica shell on the surface of poly (lactic- co -glycolic acid) (PLGA) loaded with perfluorocarbon (PFOB), hydrophobic antitumor ruthenium complex (RuPOP) and superparamagnetic Fe 3 O 4 , has been designed to achieve synchronous ultrasound (US)/magnetic resonance imaging (MR) dual mode imaging-guided HIFU-triggered chemotherapy. The introduction of PFOB in this nanosystem could cause phase transition and make it gasification to cause collapse of the outer ultrathin silicon shell under HIFU irradiation, which results in enhanced intensive mechanical stress during blasting and enhanced therapeutic effect. The blasting behavior of this nanosystem triggered by HIFU also induced the on-demand RuPOP burst release in tumor site, thus maximizing the inhibition on residual tumor induced by inhomogeneous HIFU ablation. Taken together, this treatment strategy could overcome the inevitable tumor recurrence and significantly reduces systemic side effects of HIFU, thus could be further developed for noninvasive cancer therapy. Herein an intelligent nano-bomb has been designed to achieve synchronous ultrasound/magnetic resonance dual-modality imaging-guided HIFU-triggered on-demand site-specific drug release and successful cancer ablation. Unlabelled Image • An intelligent nano-bomb with on-demand drug burst release property is designed. • The nano-bomb synergizes with HIFU to realize successful cancer ablation. • The nano-bomb achieves synchronous ultrasound/MRI dual mode imaging-guided therapy. [ABSTRACT FROM AUTHOR]

A fluorescent metal-organic framework (EuMOF) based on Eu3+ nodes coordinated by 1,1′:2′,1″-terphenyl-4,4′,4″,5′-tetracarboxylate (H4ttca) linkers has been developed as a trackable carrier with inherent fluorescence. Since Fe3O4 nanoparticles (NPs) have great value in versatile applications in vivo/vitro including imaging, cell isolation and magnetic responsivity, Fe3O4 NPs were introduced in the EuMOF composites to enhance the multifunctionalities. It has been demonstrated that the Fe3O4 NPs functionalized EuMOF composites have capability for tumor cell retrieval from matrix followed by anti-cancer drug release, which is promising to be developed as an integrated drug screening platform. Cytotoxicity was evaluated and the EuMOF-based nanocomposite exhibits significantly greater (up to 4x) biocompatibility tested on MCF-7 cells than the Zn-based MOF (the same ligand). Moreover, the EuMOF nanocarrier is capable of loading and releasing anti-cancer drugs in a controllable manner, where Doxorubicin (Dox) functionalized as a payload. Controllable release was successfully achieved after incubation with tumor cells and endocytosis analysis was obtained through the fluorescent imaging which offers monitoring of apoptosis after cargo release. Overall, fluorescent/magnetic properties of EuMOF has been investigated systematically, making it easy to be tracked in potential in vivo/vitro applications. As a drug carrier, it is biocompatible and shows highly efficient drug loading within 5 min, holding great promise in potential therapeutic delivery and other clinical applications. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles assembled from food-grade calcium carbonate have attracted attention because of their biocompatibility, digestibility, particle and surface features (such as size, surface area, and partial wettability), and stimuli-responsiveness offered by their acid-labile nature. Results: Herein, a type of edible oil-in-water Pickering emulsion was structured by calcium carbonate nanoparticles (CaCO3 NPs; mean particle size: 80 nm) and medium-chain triglyceride (MCT) for delivery of lipophilic drugs and simultaneous oral supplementation of calcium. The microstructure of the as-made CaCO3 NPs stabilized Pickering emulsion can be controlled by varying the particle concentration (c) and oil volume fraction (φ). The emulsification stabilizing capability of the CaCO3 NPs also favored the formation of high internal phase emulsion at a high φ of 0.7–0.8 with excellent emulsion stability at room temperature and at 4 °C, thus protecting the encapsulated lipophilic bioactive, vitamin D3 (VD3), against degradation. Interestingly, the structured CaCO3 NP-based Pickering emulsion displayed acid-trigged demulsification because of the disintegration of the CaCO3 NPs into Ca2+ in a simulated gastric environment, followed by efficient lipolysis of the lipid in simulated intestinal fluid. With the encapsulation and delivery of the emulsion, VD3 exhibited satisfying bioavailability after simulated gastrointestinal digestion. Conclusions: Taken together, the rationally designed CaCO3 NP emulsion system holds potential as a calcium-fortified formulation for food, pharmaceutical and biomedical applications. [ABSTRACT FROM AUTHOR]

Scavenging free radicals and reducing inflammatory reaction to relieve the secondary damage are important issues in the spinal cord injury (SCI) therapeutic strategy. Nanozymes attract more attention in the drug development of SCI due to the high stability, long-lasting catalytic capacity, and multienzyme-like properties. Herein, we constructed a Rapamycin (Rapa)-loaded and hollow mesoporous Prussian blue (HMPB)-based nanozyme (RHPAzyme) to realize the combined antioxidation and anti-inflammation combination therapy of SCI. Furthermore, activated cell penetrating peptide (ACPP) is modified onto nanozyme to endow the effectively ability of lesion area-targeting. This RHPAzyme exhibits ROS scavenging capacity with the transformation of Fe2+/Fe3+ valance and cyanide group of HMPB to achieve multienzyme-like activity. As expected, RHPAzyme scavenges the ROS overproduction and reduces inflammation in oxygen-glucose deprivation (OGD)-induced damage via inhibiting MAPK/AKT signaling pathway. Furtherly, RHPAzyme exhibits the combined antioxidant and anti-inflammatory activity in vivo , which can effectively alleviate neuronal damage and promote motor function recovery in SCI mice. Overall, this study demonstrates the RHPAzyme induces an effective treatment of SCI by inhibiting oxygen-mediated cell apoptosis and suppressing inflammation-induced injury, thus reduces the nervous impairment and promotes motor function recovery. [Display omitted] • Hollow mesoporous structure endows the stronger oxygen radical scavenging effect and higher Rapa loading capacity. • RHPAzyme achieves effectively ROS scavenging mainly attributes to the valance transformation of Fe2+/Fe3+. • RHPAzyme exhibits the dual roles of anti-oxidation and anti-inflammatory in SCI treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy is an important therapeutic modality in the treatment of cancers. Nevertheless, the characteristics of the tumor microenvironment (TME), such as hypoxia and high glutathione (GSH), limit the efficacy of radiotherapy. Manganese-based (Mn-based) nanomaterials offer a promising prospect for sensitizing radiotherapy due to their good responsiveness to the TME. In this review, we focus on the mechanisms of radiosensitization of Mn-based nanosystems, including alleviating tumor hypoxia, increasing reactive oxygen species production, increasing GSH conversion, and promoting antitumor immunity. We further illustrate the applications of these mechanisms in cancer radiotherapy, including the development and delivery of radiosensitizers, as well as their combination with other therapeutic modalities. Finally, we summarize the application of Mn-based nanosystems as contrast agents in realizing precision therapy. Hopefully, the present review will provide new insights into the biological mechanisms of Mn-based nanosystems, as well as their applications in radiotherapy, in order to address the difficulties and challenges that remain in their clinical application in the future. [ABSTRACT FROM AUTHOR]

Highlights: 2D Sn nanosheets (SnNSs) were prepared through the combination of cryogenic exfoliation and liquid-phase exfoliation. The functionalized 2D SnNSs have good stability, superior biocompatibility, high photothermal conversion efficiency, and multimode imaging capability.Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications. [ABSTRACT FROM AUTHOR]

Here, a triphenylphosphine (TPP)-labile prodrug of seleno-combretastatin-4 (CSeD) was designed and synthesized. A detailed investigation revealed that CSeD, which was shown to be very safe in circulating blood, could react with TPP to release CA-4 and a selenodiazole derivative, with accompanying powerful anticancer and antiangiogenesis effects, as well as radiosensitization properties. [ABSTRACT FROM AUTHOR]

Gallium(III)‐based drugs have gained momentum in cancer therapy due to their iron‐dependent anticancer activity. Judicious choice of ligands is critical for improved oral bioavailability, antitumor efficacy, and distinct mechanisms from simple GaIII salts. We describe GaIII complexes with planar tetradentate salen ligands [salen=2,3‐bis[(4‐dialkylamino‐2‐hydroxybenzylidene)amino]but‐2‐enedinitrile)] and labile axial solvent ligands, which display tumor growth inhibition in vitro and in vivo comparable to cisplatin. Confocal fluorescence microscopy, western blotting, mRNA profiling, chemical proteomics, and surface plasmon resonance (SPR) studies provide compelling evidence that PDIA3, a member of the protein disulfide isomerase (PDI) family involved in endoplasmic reticulum (ER) stress, is a direct target of Ga‐1. This work offers a new route to designing and synthesizing Ga‐based drugs, and also reveals that PDIA3 is an important anticancer target. [ABSTRACT FROM AUTHOR]

Gallium(III)‐based drugs have gained momentum in cancer therapy due to their iron‐dependent anticancer activity. Judicious choice of ligands is critical for improved oral bioavailability, antitumor efficacy, and distinct mechanisms from simple GaIII salts. We describe GaIII complexes with planar tetradentate salen ligands [salen=2,3‐bis[(4‐dialkylamino‐2‐hydroxybenzylidene)amino]but‐2‐enedinitrile)] and labile axial solvent ligands, which display tumor growth inhibition in vitro and in vivo comparable to cisplatin. Confocal fluorescence microscopy, western blotting, mRNA profiling, chemical proteomics, and surface plasmon resonance (SPR) studies provide compelling evidence that PDIA3, a member of the protein disulfide isomerase (PDI) family involved in endoplasmic reticulum (ER) stress, is a direct target of Ga‐1. This work offers a new route to designing and synthesizing Ga‐based drugs, and also reveals that PDIA3 is an important anticancer target. [ABSTRACT FROM AUTHOR]

The effective design of metal complexes to manipulate their lipid–water distribution coefficient is an appealing strategy for improving their cellular penetration and treatment efficacy. Here, we conveniently synthesized three iridium (Ir) complexes with red fluorescence via the simple non-conjugate modification of the side arm of the ligand. Bio-evaluation revealed that upon adding non-conjugate selenium (Se) arene derivatives, the lipid–water distribution coefficient of Ir–Se was found to be suitable, not only decreasing the toxic side effects of complexes to normal cells, but also effectively improving their anticancer activity via enhancing their penetration into tumor cells. Moreover, mechanistic investigations demonstrated that Ir–Se entered R-HeLa cells through endocytosis, and triggered apoptosis via the down-regulation of the mitochondrial membrane potential and excessive production of singlet oxygen, thereby possessing a highly effective cytotoxicity to antagonize cisplatin resistance. Therefore, we developed a convenient strategy to derive functional metal complexes and revealed that the introduction of Se on the side arm of the ligand provided the complexes with the capacity to reverse multidrug resistance. [ABSTRACT FROM AUTHOR]

O2‐delivering nanosystems have been used to antagonize hypoxia‐induced tumor therapeutic resistance. However, short‐time oxygen storage is still a bottleneck for these O2‐delivering nanosystems, which results in a decrease in blood circulation time and accumulation of oxygen in tumors, thus reducing the tumor therapeutic efficacy. Herein, a long‐term oxygen storage nanosystem (O2‐PIr@Si@PDA) is designed to overcome hypoxia for the treatment of nasopharyngeal carcinoma. This nanosystem is constructed by using perfluorooctyl bromide (PFOB) core as the oxygen carrier, functionalized with an oxygen sensitive probe (Ir(III) complex) and subsequently enclosed with an ultrathin‐walled silica shell. Due to the silica shell, this nanosystem can store oxygen for longer than 7 days. The oxygen in the O2‐PIr@Si@PDA nanosystem can be released quickly with the temperature‐responsive rupture of the silicon shell under near‐infrared (NIR) irradiation. The oxygen storage and release can be self‐monitored using the Ir(III) complex with its luminescence effect. As expected, this multifunctional nanosystem in combination with NIR irradiation not only inhibits tumor growth by alleviating hypoxia, but also enhances the effect of oxygen‐sensitized radiotherapy against nasopharyngeal carcinoma. Taken together, this study offers a novel strategy for designing long‐term oxygen storing nanosystem to relieve tumor hypoxia, thus improving the precise cancer therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells. [ABSTRACT FROM AUTHOR]

The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells. [ABSTRACT FROM AUTHOR]

Organo-seleno compounds (org-Se) have been widely used in antitumor, antiviral, and antiinflammatory therapy; antioxidation and other biological fields. As such, they have made an important contribution to overcoming various kinds of diseases, and researchers are increasingly attracted to org-Se's synthesis and functional design. This review is mainly focused on the design and synthesis of various kinds of org-Se, followed by their anticancer mechanisms such as the mitochondria mediated pathway induced by ROS, death receptor mediated pathways involving p53 phosphorylation, and the activation of the AMPK pathway to promote apoptosis. Org-Se also serves as a sensitizer in chemotherapy and radiotherapy, and an antagonist against the cytotoxic effects induced by chemotherapeutic agents. Finally, we will summarize the development of cancer-targeted org-Se containing complexes, and nanotechnology-based org-Se for anticancer application. This review could provide information for the future design of chemically innovative org-Se with anticancer potential, and shed light on the discovery of nanomaterial-based pharmaceuticals to improve drug development and formation. [ABSTRACT FROM AUTHOR]

Multifunctional nanoparticles were simply synthesized by mixing a TICT+AIE featured molecule (TPAPP‐CHO) with PBS solution. The fluorescent (FL) dots entered the cells via energy‐related endocytosis and were located in lysosome emitting green FL. This indicated that the nanoparticles were dissociated in the lysosome. Moreover, the synthesized nanoparticles (NPs) demonstrate potent cytotoxicity against human U87 glioblastoma cells by inducing cell apoptosis via triggering intracellular ROS overproduction. [ABSTRACT FROM AUTHOR]

The nitrogen and sulfur co-doped carbon dots (NSCDs) were synthesized using cysteine as precursor by hydrothermal approach, which showed good aqueous solubility, high fluorescent quantum yield (QY = 38.7%) and good photostability. The experiments with cells demonstrated that NSCDs possessed excellent biocompatibility and their cytotoxicity was low (cell viability ≥90%) in both normal and cancer cell lines. Furthermore, NSCDs as fluorescent probes could be used for the imaging of cells, which showed a good membrane permeability and strong resistance to photobleaching. In addition, the cellular uptake of NSCDs presented a time-dependent saturation. The imaging applicability of NSCDs in different cancer cells (MCF-7, A375, Hela and U251 cells) has also been demonstrated. Therefore, NSCDs are considered as promising candidates for the design of low cytotoxicity bioimaging agents and a cellular location system based on fluorescence measurements. Unlabelled Image • NSCDs show well-dispersed, high QY of 38.7% and good photostability. • NSCDs possess excellent biocompatibility in normal and cancer cell lines. • NSCDs are as fluorescent probes for cancer cell imaging and locating • The cellular uptake of NSCDs presents a time-dependent saturation. . [ABSTRACT FROM AUTHOR]