Application of artificial intelligence in cancer diagnosis and tumor nanomedicine.

Cancer is a major health concern due to its high incidence and mortality rates. Advances in cancer research, particularly in artificial intelligence (AI) and deep learning, have shown significant progress. The swift evolution of AI in healthcare, especially in tools like computer-aided diagnosis, has the potential to revolutionize early cancer detection. This technology offers improved speed, accuracy, and sensitivity, bringing a transformative impact on cancer diagnosis, treatment, and management. This paper provides a concise overview of the application of artificial intelligence in the realms of medicine and nanomedicine, with a specific emphasis on the significance and challenges associated with cancer diagnosis. It explores the pivotal role of AI in cancer diagnosis, leveraging structured, unstructured, and multimodal fusion data. Additionally, the article delves into the applications of AI in nanomedicine sensors and nano-oncology drugs. The fundamentals of deep learning and convolutional neural networks are clarified, underscoring their relevance to AI-driven cancer diagnosis. A comparative analysis is presented, highlighting the accuracy and efficiency of traditional methods juxtaposed with AI-based approaches. The discussion not only assesses the current state of AI in cancer diagnosis but also delves into the challenges faced by AI in this context. Furthermore, the article envisions the future development direction and potential application of artificial intelligence in cancer diagnosis, offering a hopeful prospect for enhanced cancer detection and improved patient prognosis.

Manganese self-boosting hollow nanoenzymes with glutathione depletion for synergistic cancer chemo-chemodynamic therapy.

Chemodynamic therapy (CDT) has outstanding potential as a combination therapy to treat cancer. However, the effectiveness of CDT in the treatment of solid tumors is limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME). GSH overexpression diminishes oxidative stress and attenuates chemotherapeutic drug-induced apoptosis in cancer cells. To counter these effects, a synergistic CDT/chemotherapy cancer treatment, involving the use of a multifunctional bioreactor of hollow manganese dioxide (HMnO2) loaded with cisplatin (CDDP), was developed. Metal nanoenzymes that can auto-degrade to produce Mn2+ exhibit Fenton-like, GSH-peroxidase-like activity, which effectively depletes GSH in the TME to attenuate the tumor antioxidant capacity. In an acidic environment, Mn2+ catalyzed the decomposition of intra-tumor H2O2 into highly toxic ·OH as a CDT. HMnO2 with large pores, pore volume, and surface area exhibited a high CDDP loading capacity (>0.6 g-1). Treatment with CDDP-loaded HMnO2 increased the intratumor Pt-DNA content, leading to the up-regulation of γ-H2Aχ and an increase in tumor tissue damage. The decreased GSH triggered by HMnO2 auto-degradation protected Mn2+-generated ·OH from scavenging to amplify oxidative stress and enhance the efficacy of CDT. The nanoenzymes with encapsulated chemotherapeutic agents deplete GSH and remodel the TME. Thus, tumor CDT/chemotherapy combination therapy is an effective therapeutic strategy.

Tryptophan catabolism via the kynurenine pathway regulates infection and inflammation: from mechanisms to biomarkers and therapies.

BACKGROUND: L-Tryptophan (L-Trp), an essential amino acid, is the only amino acid whose level is regulated specifically by immune signals. Most proportions of Trp are catabolized via the kynurenine (Kyn) pathway (KP) which has evolved to align the food availability and environmental stimulation with the host pathophysiology and behavior. Especially, the KP plays an indispensable role in balancing the immune activation and tolerance in response to pathogens. SCOPE OF REVIEW: In this review, we elucidate the underlying immunological regulatory network of Trp and its KP-dependent catabolites in the pathophysiological conditions by participating in multiple signaling pathways. Furthermore, the KP-based regulatory roles, biomarkers, and therapeutic strategies in pathologically immune disorders are summarized covering from acute to chronic infection and inflammation. MAJOR CONCLUSIONS: The immunosuppressive effects dominate the functions of KP induced-Trp depletion and KP-produced metabolites during infection and inflammation. However, the extending minor branches from the KP are not confined to the immune tolerance, instead they go forward to various functions according to the specific condition. Nevertheless, persistent efforts should be made before the clinical use of KP-based strategies to monitor and cure infectious and inflammatory diseases.

An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses.

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

hUC-MSCs therapy for Crohn's disease: efficacy in TNBS-induced colitis in rats and pilot clinical study.

BACKGROUND: The use of mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for many diseases including perianal fistulizing Crohn's disease (CD). Whether hUC-MSCs can promote the healing of luminal ulcer in CD has not been studied so far. METHODS: The model of TNBS-induced colitis in rats was used to confirm the efficacy of hUC-MSCs in the treatment of CD. Then, seventeen CD patients refractory to or unsuitable for currently available therapies were enrolled and received once submucosal local injection through colonoscopy combined with once intravenous drip on the next day. All patients received a 24-week follow-up. Clinical and laboratory assessments were monitored at baseline, week 4, 8, 12, and 24. Endoscopic evaluations were conducted at baseline and week 12. Mucosal specimens were obtained at the margin of lesions by endoscopy biopsies and used for RNA sequencing. Two hUC-MSCs co-culture systems were established in vitro, one with the mucosa specimens and the other with M1 macrophages induced from THP1. The expressions of genes representing inflammation (TNFα, IL-6, and IL-1ß) and intestinal barrier function (ZO1, CLAUDIN1, and CDH1) were tested by RT-PCR. FINDINGS: hUC-MSCs treatment increased body weight and decreased disease activity index (DAI), colon macroscopic damage index (CMDI), and histopathological score (HPS) of rats with TNBS-induced colitis. The results of the clinical study also showed that this mode of hUC-MSCs application was associated with regression of intestinal ulceration. Eight patients (47%) got endoscopic responses (SES-CD improvement of ≥50% from baseline) and three patients (17.65%) got mucosal healing (SES-CD is zero), with a parallel improvement of clinical and laboratory parameters without serious adverse events. RNA sequencing showed hUC-MSCs therapy was associated with an upregulation of transcripts linked to intestinal epithelial barrier integrity and a downregulation of inflammatory signaling pathways in the intestinal mucosa, especially the TNF signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. RNA expression of intestinal epithelial tight junction protein (ZO1, CLAUDIN1, and CDH1), and the RNA expression of major intestinal inflammatory factors in CD (IL-1ß, IL-6, and TNFα, p < 0.001 for all) were improved significantly. Moreover, hUC-MSCs could attenuate the polarization of M1 macrophage induced from THP1, thereby decreasing the mRNA expression of IL-1ß, IL-6, and TNFα significantly (p < 0.05 for all). TSG-6 expression was evaluated in hUC-MSCs culture supernatant after treatment with TNFα, IFNγ, and LPS for 48 h. And hUC-MSCs could inhibit the phosphorylation of JAK/STAT1 in the intestinal mucosa of CD patients. INTERPRETATION: hUC-MSCs transplantation alleviated TNBS-induced colitis in rats. In this pilot clinical study, preliminary data suggested that this approach to administering hUC-MSCs might have potential for clinical efficacy and manageable safety in treating refractory CD, potentially providing hope for better outcomes. No serious adverse events were observed. FUNDING: This work was funded by General Program of National Natural Science Foundation of China (Grant No. 82270639), the Scientific research project of Shanghai Municipal Health Committee (Grant No. 202240001), Specialty Feature Construction Project of Shanghai Pudong New Area Health Commission (Grant No. PWZzb2022-05), Shanghai East Hospital Youth Research and Cultivation Foundation program (Grant No. DFPY2022015), Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai, Technology Development Project of Pudong Science, Technology and Economic Commission of Shanghai (Grant No. PKJ2021-Y08), Key Disciplines Group Construction Project of Shanghai Pudong New Area Health Commission (Grant No. PWZxq2022-06), Medical discipline Construction Project of Pudong Health Committee of Shanghai (Grant No. PWYgf2021-02) and National Natural Science Foundation of China (Grant No. 82300604).

UV-assisted synthesis of ultra-small GO-Austar for efficient PTT therapeutic architectonic construction.

Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the in situ generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells in vitro. In vivo, the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.

Erythrocyte Membrane Camouflaged Nanotheranostics for Optical Molecular Imaging-Escorted Self-Oxygenation Photodynamic Therapy.

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H2 O2 ) will be decomposed by CAT to produce O2 , which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen (1 O2 ). The 1 O2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.

Deep-learning assisted zwitterionic magnetic immunochromatographic assays for multiplex diagnosis of biomarkers.

Magnetic nanoparticle (MNP)-based immunochromatographic tests (ICTs) display long-term stability and an enhanced capability for multiplex biomarker detection, surpassing conventional gold nanoparticles (AuNPs) and fluorescence-based ICTs. In this study, we innovatively developed zwitterionic silica-coated MNPs (MNP@Si-Zwit/COOH) with outstanding antifouling capabilities and effectively utilised them for the simultaneous identification of the nucleocapsid protein (N protein) of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and influenza A/B. The carboxyl-functionalised MNPs with 10% zwitterionic ligands (MNP@Si-Zwit 10/COOH) exhibited a wide linear dynamic detection range and the most pronounced signal-to-noise ratio when used as probes in the ICT. The relative limit of detection (LOD) values were achieved in 12 min by using a magnetic assay reader (MAR), with values of 0.0062 ng/mL for SARS-CoV-2 and 0.0051 and 0.0147 ng/mL, respectively, for the N protein of influenza A and influenza B. By integrating computer vision and deep learning to enhance the image processing of immunoassay results for multiplex detection, a classification accuracy in the range of 0.9672-0.9936 was achieved for evaluating the three proteins at concentrations of 0, 0.1, 1, and 10 ng/mL. The proposed MNP-based ICT for the multiplex diagnosis of biomarkers holds substantial promise for applications in both medical institutions and self-administered diagnostic settings.

Passive trapping of biomolecules in hotspots with all-dielectric terahertz metamaterials.

Electromagnetic metamaterials feature the capability of squeezing photons into hotspot regions of high intensity near-field enhancement for strong light-matter interaction, underpinning the next generation of emerging biosensors. However, randomly dispersed biomolecules around the hotspots lead to weak interactions. Here, we demonstrate an all-silicon dielectric terahertz metamaterial sensor design capable of passively trapping biomoleculars into the resonant cavities confined with powerful electric field. Specifically, multiple controllable high-quality factor resonances driven by bound states in the continuum (BIC) are realized by employing longitudinal symmetry breaking. The dielectric metamaterial sensor with nearly 15.2 experimental figure-of-merit enabling qualitative and quantitative identification of different amino acids by delivering biomolecules to the hotspots for strong light-matter interactions. It is envisioned that the presented strategy will enlighten high-performance meta-sensors design from microwaves to visible frequencies, and serve as a potential platform for microfluidic sensing, biomolecular capture, and sorting devices.

Aß-Aggregation-Generated Blue Autofluorescence Illuminates Senile Plaques as well as Complex Blood and Vascular Pathologies in Alzheimer's Disease.

Senile plaque blue autofluorescence was discovered around 40 years ago, however, its impact on Alzheimer's disease (AD) pathology has not been fully examined. We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aß aggregation in vitro. In DAPI or Hoechst staining, the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence. The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted. Both Aß self-oligomers and Aß/hemoglobin heterocomplexes generated blue autofluorescence. The Aß amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation, hemolysis, cerebral amyloid angiopathy, vascular plaques, vascular adhesions, and microaneurysms. In summary, we conclude that Aß-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer's disease.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.

Development and optimization of a frequency mixing sensor for adjacent samples quantitative detection on a lateral flow assay.

Frequency-mixing technology has been widely used to precisely identify magnetic nanoparticles in applications of quantitative biomedical detection in recent years. Examples include immune adsorption, lateral flow assays (LFAs), and biomagnetic imaging. However, the signals of magnetic response generated by adjacent magnetic samples interfere with each other owing to the small spacing between them in applications involving multi-sample detection (such as the LFA and multiplexing detection). Such signal interference prevents the biosensor from obtaining characteristic peaks related to the concentration of adjacent biomarkers from the magnetic response signals. Mathematical and physical models of the structure of sensors based on frequency-mixing techniques were developed. The theoretical model was verified and its key parameters were optimized by using simulations. A new frequency-mixing magnetic sensor structure was then designed and developed based on the model, and the key technical problem of signal crosstalk between adjacent samples was structurally solved. Finally, standard cards with stable magnetic properties were used to evaluate the performance of the sensor, and strips of the gastrin-17 (G-17) LFA were used to evaluate its potential for use in clinical applications. The results show that the minimum spacing between samples required by the optimized sensor to accurately identify them was only about 4-5 mm, and the minimum detectable concentration of G-17 was 11 pg mL-1 . This is a significant reduction in the required spacing between samples for multiplexing detection. The optimized sensor also has the potential for use in multi-channel synchronous signal acquisition, and can be used to detect synchronous magnetic signals in vivo.

Application of near-infrared fluorescence imaging in theranostics of gastrointestinal tumors.

Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients. The conventional diagnostic method is high-definition white-light endoscopy, which often leads to missed diagnosis. For surgical treatment, intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment. As a new imaging method, near-infrared fluorescence imaging (NIRFI) has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues. In this review, we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors, identification of tumor margins, identification of lymph nodes, and assessment of anastomotic leakage. In addition, we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems, and also clearly describe the application process of NIRFI from system to clinical application, and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors.

Artificial intelligence in theranostics of gastric cancer, a review.

Gastric cancer (GC) is one of the commonest cancers with high morbidity and mortality in the world. How to realize precise diagnosis and therapy of GC owns great clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in early screening, diagnosis, therapy and prognosis of stomach carcinoma. Especially AI combined with breath screening early GC system improved 97.4 % of early GC diagnosis ratio, AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18 %, specificity of 97.44 %, and sensitivity of 96.88 %. We also discuss concept, issues, approaches and challenges of AI applied in stomach cancer. This review provides a comprehensive view and roadmap for readers working in this field, with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

Integrated Smart Gas Tracking Device with Artificially Tailored Selectivity for Real-Time Monitoring Food Freshness.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.H.), as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H2S, NH3, and C2H5OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.

Immunochromatographic enhancement strategy for SARS-CoV-2 detection based on nanotechnology.

The global outbreak of coronavirus disease 2019 (COVID-19) has been catastrophic to both human health and social development. Therefore, developing highly reliable and sensitive point-of-care testing (POCT) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a priority. Among all available POCTs, the lateral flow immunoassay (LFIA, also known as immunochromatography) has proved to be effective due to its accuracy, portability, convenience, and speed. In areas with a scarcity of laboratory resources and medical personnel, the LFIA provides an affordable option for the diagnosis of COVID-19. This review offers a comprehensive overview of methods for improving the sensitivity of SARS-CoV-2 detection using immunochromatography based on nanotechnology, sorted according to the different detection targets (antigens, antibodies, and nucleic acids). It also looks into the performance and properties of the various sensitivity enhancement strategies, before delving into the remaining challenges in COVID-19 diagnosis through LFIA. Ultimately, it seeks to provide helpful guidance in selecting an appropriate strategy for SARS-CoV-2 immunochromatographic detection based on nanotechnology.

Developing an efficient MGCR microneedle nanovaccine patch for eliciting Th 1 cellular response against the SARS-CoV-2 infection.

Rationale: Novel vaccine R&D is essential to interrupt the COVID-19 pandemic and other epidemics in the future. Subunit vaccines have received tremendous attention for their low cost and safety. To improve the immunogenicity of subunit vaccines, we developed a novel vaccine adjuvant system. Methods: Here we rationally designed a CpG 1018 and graphene oxide-based bi-adjuvant system to deliver the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein and obtained the graphene oxide-based complex adjuvant nanovaccine (GCR). Furthermore, we developed a microneedle patch vaccine (MGCR) based on the GCR vaccine. Results: GCR nanovaccine displayed superb antigen loading and encapsulation efficiency. Two dosages of vaccination of GCR nanovaccine could elicit adequate RBD-specific binding antibody response with 2.14-fold higher IgG titer than Alum adjuvant vaccine. The peptide pools assay demonstrated the robust RBD-specific Type 1 Cellular response induced by the GCR nanovaccine in CD8+ T cells. Furthermore, we prepared an MGCR microneedle patch, which generated a similar RBD-specific binding antibody response to the GCR vaccine, sustained a high antibody level above 16 weeks, and significantly elevated the Tcm proportion in mouse spleen. The MGCR microneedle patch vaccine also could be stably stored at room temperature for several months and administrated without medical staff, which maximizes the vaccine distribution efficiency. Conclusion: The vaccine system could significantly improve the vaccine distribution rate in low-income areas and offer a potential vaccination approach to fight against the SARS-Cov-2 infection and other pandemics occurred in the future.

Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy.

Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal-mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H2 O2 . Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.

Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC.

BACKGROUND: There have been reports of increased glutamate pyruvate transaminase 2 (GPT2) expression in certain cancers including breast cancer. Although the role of GPT2 as a metabolic enzyme is well understood in breast cancer progression, little is known about the other roles of GPT2, especially exosomal GPT2. METHODS: BT549 and BT474 Cells were cultured and their exosomes were isolated by using ultracentrifugation. Cells migrated through the membrane were stained with crystal violet, and then were observed by microscope. Total RNA was extracted from culture cells and transcribed into cDNA, quantitative real-time RT-PCR was used to detect mRNA expression of ICAM1, VCAM1, and MMP9 using SYBR Green qPCR Mix with a 7500 Fast Real-time PCR system. Western blot was used to detect the gene expression of p-lkBa and TSG101 and GPT2 in breast cancer cells. Immunohistochemistry was used to detect the protein expression of GPT2 and BTRC in cancer cells, animal models loaded with metastasis breast cancer cells were established via tail vein injections. Interaction between GPT2 and BTRC in breast cancer cells was investigated via Co-immunoprecipitation. RESULTS: GPT2 was up-regulated in TNBC. Exosomes were isolated effectively from TNBC cells, and confirmed that GPT2 was overexpressed inexosomes. QRT-PCR showed that mRNA expression levels of ICAM1, VCAM1, and MMP9 in TNBC were high. Exosomal GPT2 derived from TNBC enhanced migration and invasion of breast cancer via in vitro cell experiment and in vivo animal model experiment. Exosomal GPT2 binds with BTRC to degrade p-lkBa, and improved metastasis of breast cancer cells. CONCLUSION: We demonstrated that GPT2 was upregulated in TNBC as well as in exosomes derived from triple-negative breast cancer (TNBC) cells. GPT2 expression was associated with the malignancy of breast cancer and promoted metastasis of breast cancer cells. Moreover, exosomal GPT2 derived from TNBC cells was verified to increase the capacity of breast cancer cells to metastasize through activating beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC). This suggested that exosomal GPT2 may be useful for breast cancer patients as a potential biomarker and treatment target.

Exploring Purification Methods of Exosomes from Different Biological Samples.

Objective: Exosomes were extracted from a variety of biological samples using several different purification processes, and our goal was to determine which method and sample were the most effective for exosome extraction. Methods: We used ExoQuick-TC combined with ultrafiltration to separate and purify exosomes from the supernatant of gastric cancer cells, while we used the ExoQuick kit and ultracentrifugation to purify exosomes from human serum samples. Furthermore, exosomes were isolated and purified from human urine samples by diafiltration and from postparturition human breast milk samples by the filtration-polyethylene glycol precipitation method. The isolated exosomes were morphologically analyzed using a transmission electron microscope, the particle size was measured by NanoSight, and the protein content was analyzed by western blotting. Results: The isolated exosomes showed an obvious cup holder shape, with a clear outline and typical exosome morphological characteristics. The sizes of exosomes derived from gastric cancer cell supernatant, serum, urine, and milk were 65.8 ± 26.9 nm, 87.6 ± 50.9 nm, 197.5 ± 55.2 nm, and 184.1 ± 68.7 nm, respectively. Western blot results showed that CD9 and TSG101 on the exosomes were expressed to varying degrees based on the exosome source. Exosome abundance was higher in the serum, urine, and breast milk than in the supernatant. It is suggested that its exosomes can be extracted to obtain an excellent potential biological source of exosomes. Conclusion: In this study, the extraction and separation methods of foreign bodies from different biological samples were obtained, and it was found that human breast milk was a potential excellent material for administration because of its high abundance.