Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

A Pt nanoenzyme- and BODIPY-loaded nanoscale covalent organic framework for relieving intratumoural hypoxia to enhance photodynamic therapy.

Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.

Ultrastructural insights into cellular organization, energy storage and ribosomal dynamics of an ammonia-oxidizing archaeon from oligotrophic oceans.

Introduction: Nitrososphaeria, formerly known as Thaumarchaeota, constitute a diverse and widespread group of ammonia-oxidizing archaea (AOA) inhabiting ubiquitously in marine and terrestrial environments, playing a pivotal role in global nitrogen cycling. Despite their importance in Earth's ecosystems, the cellular organization of AOA remains largely unexplored, leading to a significant unanswered question of how the machinery of these organisms underpins metabolic functions. Methods: In this study, we combined spherical-chromatic-aberration-corrected cryo-electron tomography (cryo-ET), scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS) to unveil the cellular organization and elemental composition of Nitrosopumilus maritimus SCM1, a representative member of marine Nitrososphaeria. Results and Discussion: Our tomograms show the native ultrastructural morphology of SCM1 and one to several dense storage granules in the cytoplasm. STEM-EDS analysis identifies two types of storage granules: one type is possibly composed of polyphosphate and the other polyhydroxyalkanoate. With precise measurements using cryo-ET, we observed low quantity and density of ribosomes in SCM1 cells, which are in alignment with the documented slow growth of AOA in laboratory cultures. Collectively, these findings provide visual evidence supporting the resilience of AOA in the vast oligotrophic marine environment.

LncRNA HOXA­AS2 is a prognostic and clinicopathological predictor in patients with cancer: A meta­analysis.

Elevated expression of long non-coding RNA homeobox A cluster antisense RNA 2 (lncRNA HOXA-AS2) is known to have prognostic value in various solid tumors. The present meta-analysis aimed to comprehensively quantify its prognostic significance across a wider spectrum of malignancies and to provide an updated synthesis of evidence that could refine prognostic models. To achieve this aim, multiple databases were carefully searched for lncRNA HOXA-AS2-related articles published in the past 10 years. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to demonstrate the prognostic value of lncRNA HOXA-AS2 using Stata 15.0 software. The function of lncRNA HOXA-AS2 was inferred from its associations with key clinical outcomes such as lymph node metastasis, distant metastasis, tumor stage and tumor size, which may reflect its role in tumor biology. In the present systematic review and meta-analysis of 454 patients across 7 studies, it was found that high lncRNA HOXA-AS2 expression was significantly associated with a shorter overall survival (OS) time in patients with cancer (HR=2.14; 95% CI, 1.40-3.27; P<0.001). High lncRNA HOXA-AS2 expression was also associated with lymph node metastasis [odds ratio (OR)=2.06; 95% CI, 1.07-3.99; P=0.032], distant metastasis (OR=2.11; 95% CI, 1.15-3.88; P=0.016), advanced tumor stage (OR=2.71; 95% CI, 1.50-4.89; P=0.001) and larger tumor size (OR=2.02; 95% CI, 0.86-4.78; P=0.006). However, no significant association was observed with age (OR=1.00; 95% CI, 0.63-1.59; P=0.991) or sex (OR=1.55; 95% CI, 0.72-3.34; P=0.258). In conclusion, elevated expression of lncRNA HOXA-AS2 was significantly related to poor clinical outcomes in various cancer types, such as osteosarcoma, non-small cell lung cancer and papillary thyroid carcinoma, a finding that was further confirmed by the present study. Specifically, the potential of lncRNAHOXA-AS2 as a biomarker in assessing tumor stage, metastasis risk and OS in patients was demonstrated. However, the results of the present study also indicated that the expression of lncRNA HOXA-AS2 was not significantly associated with age or sex, suggesting its role in cancer progression might be independent of these factors. This insight may direct future research to place more focus on the relationship between lncRNA HOXA-AS2 and specific cancer types and clinical characteristics.

Exosomal miR-361-3p promotes the viability of breast cancer cells by targeting ETV7 and BATF2 to upregulate the PAI-1/ERK pathway.

BACKGROUND: Malignant progression is the major cause of poor prognosis in breast cancer (BC) patients. Plasma exosomal miRNAs have been reported to be involved in tumor progression, but their roles in BC remain unclear. METHODS: We performed plasma exosomal miRNA sequencing on 45 individuals, including healthy controls and nonmetastatic and metastatic BC patients. We examined the correlation between miRNA expression in tumor tissues and plasma exosomes in BC patients by qRT‒PCR. The effects of exosomal miR-361-3p on BC cells were determined by CellTiter-Glo, migration and wound healing assays. The target genes of miR-361-3p and downstream pathways were explored by dual-luciferase reporter assay, RNA knockdown, rescue experiments, and western blotting. We utilized murine xenograft model to further assess the impact of plasma exosomal miR-361-3p on the malignant progression of BC. RESULTS: We found that the expression level of plasma exosomal miR-361-3p gradually increased with malignant progression in BC patients, and the expression of miR-361-3p in plasma exosomes and BC tissues was positively correlated. Consistently, exosomal miR-361-3p enhanced the migration and proliferation of two BC cell lines, MDA-MB-231 and SK-BR-3. Furthermore, our data showed that miR-361-3p inhibited two novel target genes, ETV7 and BATF2, to activate the PAI-1/ERK pathway, leading to increased BC cell viability. Finally, the consistency of the in vivo experimental results supported that elevated plasma exosomal miR-361-3p promote the malignant progression of BC. CONCLUSIONS: We found for the first time that plasma exosomal miR-361-3p was associated with malignant progression in BC patients. Mechanistically, exosomal miR-361-3p can enhance the migration and proliferation of BC cells by targeting the ETV7 and BATF2/PAI-1/ERK pathways. Our data suggest that plasma exosomal miR-361-3p has the potential to serve as a biomarker for predicting malignant progression in BC patients.

Physicochemical stability and antibacterial mechanism of theabrownins prepared from tea polyphenols catalyzed by polyphenol oxidase and peroxidase.

Tea polyphenols were used as substrates and oxidized successively by polyphenol oxidase and peroxidase to prepare theabrownins (TBs-dE). The conversion rate of catechins to TBs-dE was 90.91%. The ultraviolet and infrared spectroscopic properties and zeta potential of TBs-dE were characterized. TBs-dE is more stable at pH 5.0-7.0, about 25 °C or in dark environment. Ultraviolet light and sunlight can deepen its color due to the further oxidative polymerization. Mg2+, Cu2+, and Al3+ had a significant effect on the stability of TBs-dE. The inhibitory rates of TBs-dE (1 mg/mL) against Staphylococcus aureus and Escherichia coli DH5α were 51.45% and 45.05%, respectively. After TBs-dE treatment, the cell morphology of both bacteria changed, some cell walls were blurred, and the cytoplasmic content leaked. The research results can provide theoretical support for the industrialization of theabrownins.

Effect of Exosomes From Bone Marrow-Derived Mesenchymal Stromal Cells and Adipose-Derived Stromal Cells on Bone-Tendon Healing in a Murine Rotator Cuff Injury Model.

Background: Bone-tendon injury is characterized by poor self-healing. It is established that exosomes are favorable for tissue repair and regeneration. However, their effect on bone-tendon healing has not yet been determined. Purpose: To compare the effectiveness of exosomes derived from adipose-derived mesenchymal stromal cells (ADSC-Exos) and bone marrow-derived mesenchymal stromal cells (BMSC-Exos) on bone-tendon interface healing in murine rotator cuff injury model and explore the underlying mechanisms thereof. Study Design: Controlled laboratory study. Methods: A total of 63 male C57BL6 mice with rotator cuff injuries underwent surgery and were randomly assigned to a control group treated without exosomes (n = 21), an ADSC-Exos group (n = 21), or a BMSC-Exos group (n = 21). The mice were sacrificed 4 or 8 weeks after surgery, and tissues were collected for histologic examination and radiographic and biomechanical testing. For exosome tracing in vivo, mice were sacrificed 7 days after surgery. A series of functional assays (radiographic evaluation, proliferation assay, Alizarin Red staining, alkaline phosphatase staining and activity, Alcian blue staining, quantitative polymerase chain reaction analyses, and glycosaminoglycans quantification) were conducted to evaluate the effect of exosomes on the cellular behaviors of the BMSCs in vitro. A statistical analysis of multiple-group comparisons was performed by 1-way analysis of variance, followed by the Bonferroni post hoc test to assess the differences between the 2 groups. Results: The ADSCs and BMSCs were positive for surface markers CD29 and CD90 and negative for surface markers CD34 and CD45 and could differentiate into osteoblasts, chondrocytes, and adipocytes. Exosomes showed a cup- or sphere-shaped morphology and were positive for CD63 and TGS101. Local injection of ADSC-Exos and BMSC-Exos could recruit BMSCs and promote osteogenesis, chondrogenesis, and bone-tendon healing. In vitro, ADSC-Exos and BMSC-Exos could significantly promote the proliferation, migration, osteogenic differentiation, and chondrogenic differentiation ability of BMSCs. In vivo, ADSC-Exos and BMSC-Exos significantly accelerated bone-tendon injury healing, with no significant statistical difference between them. Conclusion: ADSC-Exos and BMSC-Exos exhibited similar therapeutic effects on bone-tendon healing in our murine animal model. Clinical Relevance: ADSC-Exos and BMSC-Exos may be used to develop a new cell-free therapy method for promoting rotator cuff injury repair.

RAB31 in glioma-derived endothelial cells promotes glioma cell invasion via extracellular vesicle-mediated enrichment of MYO1C.

Extracellular vesicles (EV), important messengers in intercellular communication, can load and transport various bioactive components and participate in different biological processes. We previously isolated glioma human endothelial cells (GhECs) and found that GhECs, rather than normal human brain endothelial cells (NhECs), exhibit specific enrichment of MYO1C into EVs and promote the migration of glioma cells. In this study, we explored the mechanism by which MYO1C is secreted into EVs. We report that such secretion is dependent on RAB31, RAB27B, and FAS. When expression of RAB31 increases, MYO1C is enriched in secretory EVs. Finally, we identified an EV export mechanism for MYO1C that promotes glioma cell invasion and is dependent on RAB31 in GhECs. In summary, our data indicate that the knockdown of RAB31 can reduce enrichment of MYO1C in extracellular vesicles, thereby attenuating the promotion of glioma cell invasion by GhEC-EVs.

The clinical value of the Duke Anesthesia Resistance Scale in predicting postoperative delirium after hip fracture surgery: a retrospective study.

Aim: This study aims to investigate the clinical value of the Duke Anesthesia Resistance Scale (DARS) in predicting postoperative delirium (POD) after hip fracture surgery. Methods: A retrospective study was conducted. Clinical data were collected from the patients who had hip fracture and underwent elective total hip arthroplasty in Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Xi'an Jiaotong University between January 2022 and June 2023. The Consciousness Fuzzy Assessment Scale was used to evaluate the occurrence of POD on postoperative day 3 (POD 3). The enrolled patients were divided into the POD group (n = 26) and the non-POD group (n = 125). Baseline characteristics, surgical data, postoperative information, and laboratory test results were collected. DARS scores were calculated using the minimum alveolar concentration, end-tidal concentration average (ETAC), and bispectral index (BIS). Multivariate logistic regression analysis was conducted to recognize the independent risk factors for POD after hip fracture surgery. Receiver operating characteristic (ROC) curve was plotted to evaluate the value of DARS in POD prediction. Results: The average age of POD group was significantly higher, comparing to non-POD group (P < 0.05). DARS scores were statistically lower in the POD group compared to non-POD group (P < 0.05). Multivariate logistic regression analysis found that age and DARS scores were factors impacting post-operative delirium occurrence after hip fracture surgery (P < 0.05). ROC showed that the area under the curve for DARS in predicting POD after hip fracture surgery was 0.929 (95% CI [0.861-0.997]). The optimal cutoff value was 30. The sensitivity was 95.45%, while the specificity was 84.09%. Conclusion: DARS score demonstrates good predictive value in hip fracture patients and is feasible in clinical practice, making it suitable for clinical application and promotion.

Physeal bar resection by modified arthroscopically assisted surgery in a closed osteocavity.

Background: Physeal bar resection has been used for partial growth arrest treatment for a decade while removing the bony bar minimally invasively and accurately is challenging. This research aims to illustrate a modified arthroscopically assisted surgery, by which all the procedure was under all-inside visualization, without the constant exchange between burring under fluoroscopy, followed by irrigation, suction, and arthroscopy of the canal. Methods: We retrospectively reviewed the patients who sustained physeal bar resection under direct all-inside visualization of the arthroscope during 2016-2021. Patients who underwent physeal bar resection with the aid of an arthroscope for identifying the physeal cartilage but not resecting and visualizing the physeal bar simultaneously were excluded from this study. Results: In total, nine patients with ten related joints were included in this study. All the patients were followed up for at least two years. The average following time was 28.5 ± 6.7 months. Eight patients with nine related joints had an improvement of angular deformity, averaging 8.3 ± 6.9 degrees, and one had a worsening of the angular deformity. All the patients had a leg length discrepancy improvement, while four patients still had LLD >1 cm. The surgery time was 3.1 ± 0.7 h. There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury. Conclusions: Using clamps to form a closed osteocavity could make physeal bar resection under all-inside arthroscopic visualization feasible, which is minimally invasive, accurate, and safe.

Risk factors and their interactive effects on severe acute pancreatitis complicated with acute gastrointestinal injury.

BACKGROUND: There are many risk factors for severe acute pancreatitis (SAP) complicated with acute gastrointestinal injury (AGI), but few reports on the interaction between these risk factors. AIM: To analyze the risk factors for SAP complicated with AGI and their interactive effects. METHODS: We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022. They were divided into AGI group and non-AGI group according to whether AGI was present. Demographic data and laboratory test data were compared between the two groups. The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression, and an analysis of the interaction of the risk factors was performed. RESULTS: The percentage of patients with multiple organ dysfunction syndrome, acute physiological and chronic health scoring system II (APACHE II) score, white blood cell count and creatinine (CRE) level was higher in the AGI group than in the non-AGI group. There was a statistically significant difference between the two groups (P < 0.05). Logistic regression analysis indicated that an APACHE II score > 15 and CRE > 100 µmol/L were risk factors for SAP complicating AGI. The interaction index of APACHE II score and CRE level was 3.123. CONCLUSION: An APACHE II score > 15 and CRE level > 100 µmol/L are independent risk factors for SAP complicated with AGI, and there is a positive interaction between them.

The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients: a systematic review and meta-analysis.

Background: Previous cohort studies have found an association between Bacillus Calmette-Guérin (BCG) administration and incident dementia. In the systematic review and meta-analysis, we aimed to summarize the current evidence of the effect of BCG use on the risk of developing dementia. Methods: We searched six databases until 20 May 2023 for studies investigating the risk of dementia and BCG administration. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were conducted as well. Results: Of the 4,043 records initially evaluated, five articles were included for final analysis, with a total of 45,407 bladder cancer (BC) patients. All five studies were evaluated and rated as with high quality, and a low possibility of publication bias was indicated. A significant association between BCG and the incidence of dementia in BC patients was found in all five studies. Although a high heterogeneity (I2 = 84.5%, p < 0.001) was observed, the pooled HR was 0.55 (0.42-0.73), indicating that BCG exposure or treatment reduced the risk of incident dementia by 45%. Moreover, the sensitivity analysis showed good robustness of the overall effect with no serious publication bias. Conclusion: BCG administration is associated with a significantly lower risk of developing dementia. However, an epidemiological cohort is needed to establish a relationship between BCG use and incident dementia in the normal population. Once the relationship is confirmed, more people may benefit from the association. Systematic review registration: identifier: CRD42023428317.

Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective. Methods: In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment. Results: Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM. Conclusion: In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research.

Investigation of the efficacy and feasibility of combined therapy of PD-L1-enhanced exogenous peripatetic adoptive natural killer (NK) cells in combination with antiangiogenic targeted therapy in the treatment of extensive-stage small cell lung cancer.

A 67-year-old male patient presented with extensive-stage small cell lung cancer with the primary lesion located in the right upper lung, accompanied by multiple metastases to the pleura and abdominal cavity with enlarged mediastinal lymph nodes. A combination therapy approach was used to target the patient's multiple systemic metastases after localized radiotherapy. The approach involved adoptive transfer of programmed death ligand 1 (PD-L1) enhanced exogenous natural killer (NK) cells, along with antiangiogenic treatment. Allogeneic cord blood NK cells were infused back into the patient over two consecutive days. On the first day, the treatment was followed by a dose of 1200 mg of atezolizumab. Subsequently, the patient received a daily dose of 10 mg of anlotinib administered orally for 14 days. This was followed by a 7-day break, and each cycle lasted 21 days. After delivering localized radiation to the primary lesion in the right lung and metastatic mediastinal lymph nodes, complete remission was achieved in the local lesion, effectively avoiding the risk of superior vena cava syndrome. Following six cycles of combined therapy, most of the metastatic lesions had disappeared, and the remaining metastatic lesions had significantly reduced in size. The recent therapeutic effect resulted in partial remission. The combination therapy of immune checkpoint inhibitor PD-L1-enhanced exogenous adoptive transfer NK cells, along with antiangiogenic targeted treatment, demonstrated a satisfactory short-term effect, with disappearance of most of the metastases and noticeable shrinkage in the remaining metastatic lesions.

DNA Methylation in Alcohol Use Disorder.

Excessive drinking damages the central nervous system of individuals and can even cause alcohol use disorder (AUD). AUD is regulated by both genetic and environmental factors. Genes determine susceptibility to alcohol, and the dysregulation of epigenome drives the abnormal transcription program and promotes the occurrence and development of AUD. DNA methylation is one of the earliest and most widely studied epigenetic mechanisms that can be inherited stably. In ontogeny, DNA methylation pattern is a dynamic process, showing differences and characteristics at different stages. DNA dysmethylation is prevalent in human cancer and alcohol-related psychiatric disorders, resulting in local hypermethylation and transcriptional silencing of related genes. Here, we summarize recent findings on the roles and regulatory mechanisms of DNA methylation, the development of methyltransferase inhibitors, methylation alteration during alcohol exposure at different stages of life, and possible therapeutic options for targeting methylation in human and animal studies.

A bioresponsive diselenide-functionalized hydrogel with cascade catalytic activities for enhanced local starvation- and hypoxia-activated melanoma therapy.

Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H2O2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. STATEMENT OF SIGNIFICANCE: There has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment.

Self-Propelled Enzymatic Nanomotors from Prodrug-Skeletal Zeolitic Imidazolate Frameworks for Boosting Multimodel Cancer Therapy Efficiency.

Self-propelled nanomotors, which can autonomous propelled by harnessing others type of energy, have shown tremendous potential as drug delivery systems for cancer therapy. However, it remains challenging for nanomotors in tumor theranostics because of their structural complexity and deficient therapeutic model. Herein, glucose-fueled enzymatic nanomotors (GC6@cPt ZIFs) are developed through encapsulation of glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) using cisplatin-skeletal zeolitic imidazolate frameworks (cPt ZIFs) for synergetic photochemotherapy. The GC6@cPt ZIFs nanomotors can produce O2 through enzymatic cascade reactions for propelling the self-propulsion. Trans-well chamber and multicellular tumor spheroids experiments demonstrate the deep penetration and high accumulation of GC6@cPt nanomotors. Importantly, the glucose-fueled nanomotor can release the chemotherapeutic cPt and generate reactive oxygen species under laser irradiation, and simultaneously consume intratumoral over-expressed glutathione. Mechanistically, such processes can inhibit cancer cell energy and destroy intratumoral redox balance to synergistically damage DNA and induce tumor cell apoptosis. Collectively, this work demonstrates that the self-propelled prodrug-skeleton nanomotors with oxidative stress activation can highlight a robust therapeutic capability of oxidants amplification and glutathione depletion to boost the synergetic cancer therapy efficiency.

A covalent organic framework-based nanoreactor for enhanced photothermal therapy via inhibiting intracellular heat defense systems.

Herein, we report an indocyanine green (ICG)-decorated and glucose oxidase (GOx)-loaded nanoscale composite COF material via a stepwise post-synthetic modification. The obtained GOx@COF-ICG can achieve synergistic inhibition of intracellular heat defense systems through starvation therapy to enhance photothermal therapy of tumors.

A reactive oxygen species-responsive covalent organic framework for tumor combination therapy.

Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (1O2)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.