A one-two punch strategy for diabetic wound management based on an antibiotic-hybrid biomineralized iron sulfide nanoparticle.

Bacterial infection and immune imbalance are the primary culprits behind chronic wounds in individuals with diabetes, impeding the progression of damaged tissues towards normal healing. To achieve a harmonious balance between pro- and anti-inflammation within these infected areas, herein, we propose a one-two punch strategy for on-demand therapy of diabetes-infected wounds, utilizing an azithromycin (AZM)-hybrid nanocomposite termed GOx@FexSy/AZM. During the infective stage, the nanocomposite facilitates the production of ROS, coupled with the burst release of AZM and H2S gas, effectively dismantling biofilms and achieving rapid sterilization. Subsequently, the hyperinflammatory response induced by antibiosis is significantly mitigated through the synergistic action of tissue H2S and the prolonged half-life of AZM. These components inhibit the activity of pro-inflammatory transcription factors (AP-1 and NF-κB) within macrophages, thereby promoting the polarization of macrophages towards a reparative M2 phenotype and facilitating tissue remodeling. By catering to the diverse requirements of wound healing at different stages, this nanocomposite accelerates a sensible transition from inflammation to the reparative phase. In summary, this one-two punch strategy gives an instructive instance for procedural treatment of diabetes wound infection. STATEMENT OF SIGNIFICANCE: The treatment of diabetic wound infection presents two major challenges: the diminished antibacterial efficacy arising from biofilm formation and bacterial resistance, as well as the inadequate transition of the wound microenvironment from pro-inflammatory to anti-inflammatory states after bacterial clearance. In this work, a biomineralized iron sulfide nanocomposite was prepared to mediate cascade catalytic (ROS storm) / antibiotic (AZM) / gas (H2S) triple-synergetic antibacterial therapy during the initial stage of bacterial infection, achieving the goal of rapid bactericidal effect; Subsequently, the residual H2S and long half-life AZM would inhibit the key pro-inflammatory transcription factors and promote the macrophages polarization to reparative M2, which effectively mediated tissue repair after hyperinflammatory reactions, leading to orderly treatment of hyperglycemic infected wounds.

LCN2 Promotes Proliferation and Glycolysis by Activating the JAK2/STAT3 Signaling Pathway in Hepatocellular Carcinoma.

This study aimed to explore the molecular mechanism of LCN2 regulating aerobic glycolysis on abnormal proliferation of HCC cells. Based on the prediction of GEPIA database, the expression levels of LCN2 in hepatocellular carcinoma tissues were detected by RT-qPCR analysis, western blot, and immunohistochemical staining, respectively. In addition, CCK-8 kit, clone formation, and EdU staining were used to analyze the effect of LCN2 on the proliferation of hepatocellular carcinoma cells. Glucose uptake and lactate production were detected using kits. In addition, western blot was used to detect the expressions of aerobic glycolysis-related proteins. Finally, western blot was used to detect the expressions of phosphorylation of JAK2 and STAT3. We found LCN2 was upregualted in hepatocellular carcinoma tissues. CCK-8 kit, clone formation, and EdU staining results showed that LCN2 could promote the proliferation in hepatocellular carcinoma cells (Huh7 and HCCLM3 cells). Western blot results and kits confirmed that LCN2 significantly promotes aerobic glycolysis in hepatocellular carcinoma cells. Western blot results showed that LCN2 could significantly upregulate the phosphorylation of JAK2 and STAT3. Our results indicated that LCN2 activated the JAK2/STAT3 signaling pathway, promoted aerobic glycolysis, and accelerated malignant proliferation of hepatocellular carcinoma cells.

Clinical study of early rehabilitation training combined with negative pressure wound therapy for the treatment of deep partial-thickness hand burns.

Objective: This study aims to explore the clinical effect of early rehabilitation training combined with negative pressure wound therapy (NPWT) for treating deep partial-thickness hand burns. Methods: Twenty patients with deep partial-thickness hand burns were randomly divided into an experimental group (n = 10) and a control group (n = 10). In the experimental group, early rehabilitation training combined with NPWT was performed, including the proper sealing of the negative pressure device, intraoperative plastic brace, early postoperative exercise therapy during negative pressure treatment, and intraoperative and postoperative body positioning. Routine NPWT was conducted in the control group. Both groups received 4 weeks of rehabilitation after wounds healed by NPWT with or without skin grafts. Hand function was evaluated after wound healing and 4 weeks after rehabilitation, including hand joint total active motion (TAM) and the brief Michigan Hand Questionnaire (bMHQ). Results: Twenty patients were involved in this study, including 16 men and 4 women, aged 18-70 years, and the hand burn area ranged from 0.5% to 2% of the total body surface area (TBSA). There was no significant difference in TAM and bMHQ scores between the two groups after negative pressure removal. After 4 weeks of rehabilitation training, the TAM scores and bMHQ scores were significantly improved in both groups (p < 0.05); among them, those of the experimental group were both significantly better than those of the control group (p < 0.05). Conclusion: The application of early rehabilitation training combined with NPWT to treat deep partial-thickness hand burns can effectively improve hand function.

Reporter Genes for Brain Imaging Using MRI, SPECT and PET.

The use of molecular imaging technologies for brain imaging can not only play an important supporting role in disease diagnosis and treatment but can also be used to deeply study brain functions. Recently, with the support of reporter gene technology, optical imaging has achieved a breakthrough in brain function studies at the molecular level. Reporter gene technology based on traditional clinical imaging modalities is also expanding. By benefiting from the deeper imaging depths and wider imaging ranges now possible, these methods have led to breakthroughs in preclinical and clinical research. This article focuses on the applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies for use in brain imaging. The tracking of cell therapies and gene therapies is the most successful and widely used application of these techniques. Meanwhile, breakthroughs have been achieved in the research and development of reporter genes and their imaging probe pairs with respect to brain function research. This paper introduces the imaging principles and classifications of the reporter gene technologies of these imaging modalities, lists the relevant brain imaging applications, reviews their characteristics, and discusses the opportunities and challenges faced by clinical imaging modalities based on reporter gene technology. The conclusion is provided in the last section.

Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues.

The ability to effectively detect bacterial infection in human tissues is important for the timely treatment of the infection. However, traditional techniques fail to visualize bacterial species adhered to host cells in situ in a target-specific manner. Dihydropteroate synthase (DHPS) exclusively exists in bacterial species and metabolically converts p-aminobenzoic acid (PABA) to folic acid (FA). By targeting this bacterium-specific metabolism, we have developed a fluorescent imaging probe, PABA-DCM, based on the conjugation of PABA with a long-wavelength fluorophore, dicyanomethylene 4H-pyran (DCM). We confirmed that the probe can be used in the synthetic pathway of a broad spectrum of Gram-positive and negative bacteria, resulting in a significantly extended retention time in bacterial over mammalian cells. We validated that DHPS catalytically introduces a dihydropteridine group to the amino end of the PABA motif of PABA-DCM, and the resulting adduct leads to an increase in the FA levels of bacteria. We also constructed a hydrogel dressing containing PABA-DCM and graphene oxide (GO), termed PABA-DCM@GO, that achieves target-specific fluorescence visualization of bacterial infection on the wounded tissues of mice. Our research paves the way for the development of fluorescent imaging agents that target species-conserved metabolic pathways of microorganisms for the in situ monitoring of infections in human tissues.

Molecular Identification and Phylogenetic Analysis of Ascarids in Wild Animals.

Ascarid nematodes are the most common and harmful nematodes parasites in animals. By analyzing genetic variation, this study explores the genetic and phylogenetic relationship among ascarids from 11 different hosts. This study collected ascarid samples from the feces of nine animal species in Changsha Ecological Zoo of Hunan Province and two animal kinds in the College of Veterinary Medicine of Hunan Agricultural University. The mitochondrial gene (pcox1) and ribosomal ITS sequences were amplified, sequenced, and analyzed by PCR to identify the species of the samples. The phylogenetic tree was constructed based on two genes (cox1 and ITS) by the Neighbor-joining method, and the phylogenetic relationship was analyzed. The sequencing results showed that the sequence lengths of pcox1 and ITS genes in the samples were 441 bp and 838-1,177 bp, respectively. The difference rates were 0.00-1.70% in pcox1 gene and 0.00-7.30% in ITS gene. Phylogenetic analysis showed that ascarid worms from the white lion, Northeast tiger, South China tiger and cheetah were identified as Toxascaris leonina. Ascarids from the zebra were identified as Parascaris equorum, while those from chicken and peacocks were identified as Ascaridia galli. Ascarids of wolf and dog origin were Toxocara canis, the snake ascarids belonged to Ophidascaris filaria, and the bear ascarids belonged to Baylisascaris transfuga. There was a significant gap between different kinds of ascarid worms. We found that these two mitochondrial genes pcox1 and ITS showed a common characteristic that the intraspecific differences were significantly smaller than the interspecific differences, confirming that these two genes could be used as interspecific genetic markers for molecular identification of different ascarids origins. The intraspecific variation rate of the ITS gene was higher than that of pcox1, indicating that ITS can also be used in the genetic research of Ascaris species development. This study revealed the genetic evolution and phylogeny of ascarids in wild animals, and our results will help prevent and control ascarids in wild animals.

Lentivirus-mediated subcutaneous JAM-A modification promotes skin wound healing in a mouse model by strengthening the secretory function and proliferation of fibroblasts.

A better understanding of the molecular regulation of wound healing may provide novel therapeutic targets. A previous study revealed that junctional adhesion molecule A (JAM-A)-modified mesenchymal stem cells promoted wound healing. However, whether direct JAM-A modification in the skin wound edge area accelerates the wound repair process is not clear. We determined whether JAM-A modification at the skin wound edge accelerated the wound healing process. We established JAM-A modification mouse wound models and mouse primary fibroblast cell models. Wound pictures were taken to compare the wound size. H&E staining was performed to monitor the morphology of the wound and quality of the newborn skin. CCK-8 assays and immunofluorescence (IF) for Ki67 were used to measure the cell proliferation of mouse primary fibroblasts. Quantitative real-time PCR, immunohistochemistry, IF, and Western blot analysis were used to detect bFGF and EGF expression in vivo and in vitro. The JAM-A-overexpressing group exhibited a smaller residual wound size than the control group at Day 7. Thicker epidermal layers and more hair follicle-like structures were found in the JAM-A-overexpressing group at Day 21. Cell proliferation capacity was higher in JAM-A-modified mouse fibroblasts. Elevated levels of bFGF and EGF were found in the JAM-A-modified group in vivo and in vitro. JAM-A modification significantly promoted fibroblast proliferation and wound healing. Increased levels of bFGF and EGF growth factors may be part of the mechanism.

Molecular Characterization and Phylogenetic Analysis of Spirometra Tapeworms from Snakes in Hunan Province.

Sparganosis is a neglected zoonotic parasitic disease that poses huge threats to humans worldwide. Snakes play an important role in sparganosis transmission because they are the most common second intermediate hosts for Spirometra parasites. However, the population genetics of Spirometra isolates from snakes is currently not well studied in China. The present study was performed to explore the molecular characteristics and phylogenetic analysis of Spirometra tapeworms from different species of snakes in Hunan Province. This study obtained 49 Spirometra isolates from 15 geographical areas in Hunan Province, Central China. Subsequently, the 18S and 28S ribosomal DNA (rDNA) fragments were amplified from the isolated parasites, and their sequences were analyzed to assess their genetic diversity. Phylogenetic analyses were performed using the maximum likelihood algorithm. The results showed that sequence variations among these isolates were 0-2.3% and 0-0.1% for 18S and 28S rDNA, respectively. The phylogenetic analysis showed that all Spirometra isolates from Hunan Province were clustered into the same branch with Spirometra erinaceieuropaei isolated from other areas (China, Vietnam, Australia). Moreover, the phylogenetic trees revealed that Spirometra is closely related to Adenocephalus, Pyramicocephalus, Ligula, Dibothriocephalus, Schistocephalus, and Diphyllobothrium. The Spirometra isolates of different hosts/regions in Hunan Province are not host segregated or geographically isolated, and support for the taxonomic status of Spirometra tapeworms in China has been added. These results provide reference values for future accurate identification and taxonomic status of Spirometra tapeworms in China.

Enzyme-Responsive Materials as Carriers for Improving Photodynamic Therapy.

Photodynamic therapy (PDT) is a mini-invasive therapy on malignancies via reactive oxygen species (ROS) induced by photosenitizer (PS) upon light irradiation. However, poor target of PS to tumor limits the clinical application of PDT. Compared with normal tissues, tumor tissues have a unique enzymatic environment. The unique enzymatic environment in tumor tissues has been widely used as a target for developing smart materials to improve the targetability of drugs to tumor. Enzyme-responsive materials (ERM) as a smart material can respond to the enzymes in tumor tissues to specifically deliver drugs. In PDT, ERM was designed to react with the enzymes highly expressed in tumor tissues to deliver PS in the target site to prevent therapeutic effects and avoid its side-effects. In the present paper, we will review the application of ERM in PDT and discuss the challenges of ERM as carriers to deliver PS for further boosting the development of PDT in the management of malignancies.

Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations.

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH•+), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH•+ releasing H• [denoted as ΔG HD o(XRH•+) and ΔG HD ≠(XRH•+)] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH2) and NADH. ΔG HD o(XRH•+) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). ΔG HD ≠(XRH•+) range from 29.81 to 39.00 kcal/mol, indicating that XRH•+ spontaneously releasing H• are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH•+) releasing H• [ΔG HD o(DPH•+) and ΔG HD ≠(DPH•+)] should be 19-32 kcal/mol and 29-39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [ΔG HD o(XRH•+)] and the activation free energy [ΔG HD ≠(XRH•+)] are also explored. Gibbs free energy is the important and decisive parameter, and ΔG HD ≠(XRH•+) increases in company with the increase of ΔG HD o(XRH•+), but no simple linear correlations are found. Even though all XRH•+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH•+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH•+ with nonaromatic substituents tend to release R• instead of H• to quench radicals. XRH•+ with aromatic substituents tend to release H• and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.

ZIF-Based Nanoparticles Combine X-Ray-Induced Nitrosative Stress with Autophagy Management for Hypoxic Prostate Cancer Therapy.

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2- ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2- , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.

An in situ approach to functionalize metal-organic frameworks with tertiary aliphatic amino groups.

Metal-catalyzed reductive amination of formyl-containing linkers with N,N-dialkylformamide solvents is concomitant with the solvothermal coordination assembly, leading to novel MOFs functionalized with tertiary aliphatic amino groups. This illustrates a novel one-pot strategy to functionalize MOFs through in situ organic transformation. The UiO-66 MOFs partially functionalized with the amino groups are highly active heterogeneous catalysts for Knoevenagel condensation.

Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function.

BACKGROUND: Diabetic wounds are one of the most common and serious complications of diabetes mellitus, characterized by the dysfunction of wound-healing-related cells in quantity and quality. Our previous studies revealed that human amniotic epithelial cells (hAECs) could promote diabetic wound healing by paracrine action. Interestingly, numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy. However, whether exosomes derived from hAECs (hAECs-Exos) mediate the effects of hAECs on diabetic wound healing remains unclear. This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism. METHODS: hAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy, dynamic light scattering and flow cytometry. A series of in vitro functional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts (HFBs) and human umbilical vein endothelial cells (HUVECs) in a high-glycemic microenvironment. High-throughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs. Subsequently, the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs, as well as in diabetic wound healing, was assessed. RESULTS: hAECs-Exos presented a cup- or sphere-shaped morphology with a mean diameter of 105.89 ± 10.36 nm, were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs. After that, hAECs-Exos not only significantly promoted the proliferation and migration of HFBs, but also facilitated the angiogenic activity of HUVECs in vitro. High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway. Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs, as well as on wound healing, in diabetic mice. CONCLUSIONS: Our findings demonstrated that hAECs-Exos represent a promising, novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway.

Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme-Loaded Electrophilic ZIFs.

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS-mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF-82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS-mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework-82 (ZIF-82@CAT Dz) shell can be degraded into Zn2+ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H2 O2 accumulation. These "disordered" cells show reduced resistance to ROS and are effectively killed by ferrous cysteine-phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H2 O2 triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS-mediated treatment of hypoxic tumors.

Near-Infrared Light-Triggered Chlorine Radical (. Cl) Stress for Cancer Therapy.

Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2 O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (. Cl) nano-generator with SiO2 -coated upconversion nanoparticles (UCNPs) on the inside and Ag0 /AgCl hetero-dots on the outside. Upon near-infrared (NIR) light irradiation, the short-wavelength emission UCNP catalyzes . Cl generation from Ag0 /AgCl with no dependence on O2 /H2 O2 . . Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This . Cl stress treatment will no doubt broaden the family of oxidative stress-induced antitumor strategies by using non-oxygen free radicals, which is significant in the development of new anticancer agents.

Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I-TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the O-H bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine.

Accurate and Real-Time Temperature Monitoring during MR Imaging Guided PTT.

Photothermal therapy (PTT) is an efficient approach for cancer treatment. However, accurately monitoring the spatial distribution of photothermal transducing agents (PTAs) and mapping the real-time temperature change in tumor and peritumoral normal tissue remain a huge challenge. Here, we propose an innovative strategy to integrate T1-MRI for precisely tracking PTAs with magnetic resonance temperature imaging (MRTI) for real-time monitoring temperature change in vivo during PTT. NaBiF4: Gd@PDA@PEG nanomaterials were synthesized with favorable T1-weighted performance to target tumor and localize PTAs. The extremely weak susceptibility (1.04 × 10-6 emu g-1 Oe1-) of NaBiF4: Gd@PDA@PEG interferes with the local phase marginally, which maintains the capability of MRTI to dynamically record real-time temperature change in tumor and peritumoral normal tissue. The time resolution is 19 s per frame, and the detection precision of temperature change is approximately 0.1 K. The approach achieving PTT guided by multimode MRI holds significant potential for the clinical application.

Full-Process Radiosensitization Based on Nanoscale Metal-Organic Frameworks.

Full-process radiosensitization, that is, pre-increasing radiation sensitivity of cancer cells, magnifying •OH formation during ionizing irradiation, and intervention on the resultant DNA repair for final cells death, could enhance the overall radiotherapeutic effects, but has not yet been achieved. Herein, Hf-nMOFs with Fe3+ ions uniformly dispersed (Hf-BPY-Fe) were constructed to integratedly improve radiotherapeutic effects via a multifaceted mechanism. The in vitro experiments demonstrated that persistent reactive oxygen species stress from Hf-BPY-Fe-activated in situ Fenton reaction reassorted cell cycle distribution, consequently contributing to increased tumoral radiosensitivity to photon radiation. Upon irradiation during the course of radiation therapy, Hf4+ in Hf-BPY-Fe gave substantial amounts of high-energy electrons, which partially converted H2O to •OH and, meanwhile, relaxed to a low-energy state in nMOF pores, leading to an electron-rich environment. These aggregated electrons facilitated the reduction from Fe3+ to Fe2+ and further promoted the production of •OH in the Fenton process to attack DNA. The Hf-BPY-Fe postponed the DNA damage response process by interfering with certain proteins involved in the DNA repair signaling pathway. The in vivo experiments showed improved radiotherapeutic effects from integrated contributions from Fe3+-based Fenton reaction and Hf4+-induced X-ray energy conversion in tumors. This work provides a nMOFs-based full-process radiosensitizing approach for better radiotherapeutic efficacy.

Cathodic protected Mn2+ by NaxWO3 nanorods for stable magnetic resonance imaging-guided tumor photothermal therapy.

The stability and safety of magnetic resonance imaging (MRI) contrast agents (CAs) are crucial for accurate diagnosis and real-time monitor of tumor development. Paramagnetic Mn2+ as nonlanthanide metal ion has been widely studied for use in T1-MRI CAs, but unfortunately, Mn2+ can be oxidized by H2O2 in tumor to nonparamagnetic Mn4+ via a Fenton-like reaction. The concurrent loss of paramagnetism and production of toxic hydroxyl radical (OH) go against the basic requirment of CAs, thus restricting the further development of Mn2+-based CAs. Based on the different standard potential of W6+/W5+ (~0.26 V) and Mn4+/Mn2+ (~1.2 V), a "cathodic protection" strategy was exploited in Mn2+-doped NaxWO3 nanorods (NaxMnWO3), with W5+ as the sacrificial anode and Mn2+ as the protected cathode, to protect Mn2+ from oxidation in tumor for stable MR contrast performance, as well as repress its Fenton-like reaction activity for good biosafety. Moreover, the tungsten bronze crystal structure endows NaxMnWO3 with excellent near-infrared (NIR)-photothermal properties for effective tumor hyperthermia, without effect from the changed oxidation state of W. This "cathodic protection" strategy offers a new method for the development of reliable and hypotoxic biomaterials for stable imaging and therapeutic applications in clinic.

Magnetic resonance energy transfer for in vivo glutathione susceptibility weighted imaging.

Glutathione (GSH) plays a vital role in maintaining biological redox homeostasis. Accordingly, accurate imaging of glutathione in vivo is of great significance. Herein, we propose a magnetic resonance energy transfer (MRET) strategy based on a distance-dependent magnetic exchange coupling effect (MECE), which can realize GSH detection within tumors in vivo by susceptibility weighted imaging (SWI). Fe3O4 nanoparticles (NPs) and CoFe2O4 NPs linked with cystamine (Fe3O4-S-S-CoFe2O4) have been successfully designed as SWI nanoprobes. After the disulfide bonds are broken by excess GSH in the tumor, the increase in the distance between Fe3O4 NPs and CoFe2O4 NPs will induce a decrease of MECE and magnetic susceptibility. As a result, the changes in the SWI signals are used for tumor GSH detection in vivo. Experimental results in vitro and in vivo demonstrate that the Fe3O4-S-S-CoFe2O4 SWI nanoprobe can sensitively detect concentrations of GSH in tumors. Hence, this strategy not only improves the sensitivity of the GSH response in SWI but also provides a powerful basis for the design of other responsive functional MRI nanoprobes.