Photo-Activated Oxidative Stress Amplifier: A Strategy for Targeting Glutathione Metabolism and Enhancing ROS-Mediated Therapy in Triple-Negative Breast Cancer Treatment.

Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC). Therefore, the development of innovative nanomedicines that can effectively disrupt the redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an oxidative stress amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme and a CaP mineralized layer, loaded with GSH inhibitor L-buthionine sulfoximine (BSO), and further surface-modified with hyaluronic acid that can target CD44, is introduced. In the acidic tumor microenvironment, Ca2+ is initially released, thereby leading to mitochondrial dysfunction and eventually triggering apoptosis. Additionally, BSO suppresses the synthesis of intracellular reduced GSH and further amplifies the level of oxidative stress in cancer cells. Furthermore, PdAg nanozyme can be activated by near-infrared light to induce photothermal and photodynamic effects, causing a burst of ROS and simultaneously promoting cell apoptosis via provoking immunogenic cell death. The high-performance therapeutic effects of PBCH, based on the synergistic effect of aforementioned multiple oxidative damage and photothermal ablation, are validated in TNBC cells and animal models, declaring its potential as a safe and effective anti-tumor agent. The proposed approach offers new perspectives for precise and efficient treatment of TNBC.

Metal ion interference therapy: metal-based nanomaterial-mediated mechanisms and strategies to boost intracellular "ion overload" for cancer treatment.

Metal ion interference therapy (MIIT) has emerged as a promising approach in the field of nanomedicine for combatting cancer. With advancements in nanotechnology and tumor targeting-related strategies, sophisticated nanoplatforms have emerged to facilitate efficient MIIT in xenografted mouse models. However, the diverse range of metal ions and the intricacies of cellular metabolism have presented challenges in fully understanding this therapeutic approach, thereby impeding its progress. Thus, to address these issues, various amplification strategies focusing on ionic homeostasis and cancer cell metabolism have been devised to enhance MIIT efficacy. In this review, the remarkable progress in Fe, Cu, Ca, and Zn ion interference nanomedicines and understanding their intrinsic mechanism is summarized with particular emphasis on the types of amplification strategies employed to strengthen MIIT. The aim is to inspire an in-depth understanding of MIIT and provide guidance and ideas for the construction of more powerful nanoplatforms. Finally, the related challenges and prospects of this emerging treatment are discussed to pave the way for the next generation of cancer treatments and achieve the desired efficacy in patients.

Serine protease Rv2569c facilitates transmission of Mycobacterium tuberculosis via disrupting the epithelial barrier by cleaving E-cadherin.

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall-associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

Boosting Sono-immunotherapy of Prostate Carcinoma through Amplifying Domino-Effect of Mitochondrial Oxidative Stress Using Biodegradable Cascade-Targeting Nanocomposites.

Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8+ T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.

Squalene monooxygenase facilitates bladder cancer development in part by regulating PCNA.

Bladder cancer (BC) is one of the most common cancers worldwide. Although the treatment and survival rate of BC are being improved, the risk factors and the underlying mechanisms causing BC are incompletely understood. Squalene monooxygenase (SQLE) has been associated with the occurrence and development of multiple cancers but whether it contributes to BC development is unclear. In this study, we performed bioinformatics analysis on paired BC and adjacent non-cancerous tissues and found that SQLE expression is significantly upregulated in BC samples. Knockdown of SQLE impairs viability, induces apoptosis, and inhibits the migration and invasion of BC cells. RNA-seq data reveals that SQLE deficiency leads to dysregulated expression of genes regulating proliferation, migration, and apoptosis. Mass spectrometry-directed interactome screening identifies proliferating cell nuclear antigen (PCNA) as an SQLE-interacting protein and overexpression of PCNA partially rescues the impaired viability, migration, and invasion of BC cells caused by SQLE knockdown. In addition, we performed xenograft assays and confirmed that SQLE deficiency inhibits BC growth in vivo. In conclusion, these data suggest that SQLE promotes BC development and SQLE inhibition may be therapeutically useful in BC treatment.

Serum VEGF as a predictive marker of glycemic control and diabetic nephropathy in Chinese older adults with type 2 diabetes mellitus.

Objectives: Recent researches have demonstrated good correlation between vascular endothelial growth factor (VEGF) and diabetic nephropathy (DN); however, this relationship seems less clear-cut when VEGF was measured in blood samples. We tended to explore the possible association between serum VEGF and glycemic control and diabetic nephropathy severity in Chinese older adults with type 2 diabetes mellitus (T2DM). Materials and methods: This study retrospectively enrolled 595 older T2DM adults at random. Participants were clinically grouped across the urine albumin-to-creatinine ratio (UACR) and the HbA1c tertiles by genders. Linear regressions were performed for the correlation of VEGF with HbA1c and UACR and binary logistic regressions for the odds of DN after adjusting for confounders. The receiver operating characteristic (ROC) curves were conducted for the predictive value of VEGF for DN. Results: Both males and females with DN exhibited higher VEGF levels than non-DN (P < 0.001). Furthermore, a positive correlation of VEGF with UACR and HbA1c was presented regardless of adjusting confounding factors (P < 0.001). Serum VEGF level and fasting plasma glucose (FPG) were independent risk factors of DN in older adults of both genders (P < 0.05), while the risk prediction of DN by HbA1c only reflected in female patients (P < 0.05). The ROC curve of VEGF for DN had the area under curve (AUC) of 0.819 for males and 0.793 for females, indicating the clinical value of serum VEGF as a predictive biomarker. Conclusions: Serum VEGF was strongly associated with UACR and HbA1c in both genders, and could be regarded as a predictive biomarker for glycemic control and diabetic nephropathy in older adults with T2DM.

Endoscopic ultrasound-guided injection of carbon nanoparticles suspension to label rectal cancer before neoadjuvant chemoradiotherapy: a retrospective cohort study.

Background: Localization of the primary tumor and ensuring safe distal surgical margins (DSMs) following neoadjuvant chemoradiotherapy (nCRT) are challenging in locally advanced rectal cancers (LARCs). This study investigated the effectiveness of carbon nanoparticles suspension (CNS) for labeling the primary tumor and allowing precise tumor resection after nCRT. Methods: Clinicopathological data of LARC patients who underwent nCRT followed by laparoscopic radical anal preservation surgery at our center between January 2018 and February 2023 were prospectively collected. The patients were divided into the CNS tattooed (CNS) and non-tattooed (control) groups. In the CNS group, CNS was injected in four quadrants on the anal side 1 cm away from the lower tumor margin. DSMs were determined through intraoperative distal rectal examination in the control group and observation of CNS tattoos in the CNS group. DSM lengths and positive DSM rates were compared between the two groups to analyse the feasibility and effectiveness of CNS for labeling LARCs before nCRT. Results: There was no statistically significant difference in the basic demographic data, effectiveness of nCRT, or post-operative recovery rates between the two groups (all P > 0.05). In the CNS group, CNS tattoos were observed on the outside of the rectal wall, with an overall efficiency of 87.1% (27/31). The CNS group had fewer positive DSMs and safer DSM lengths (2.73 ± 0.88 vs 2.12 ± 1.15 cm, P = 0.012) than the control group (P < 0.05). Conclusions: Endoscopic ultrasound-guided injection of CNS tattoos before nCRT could effectively label the LARCs, ensuring safe DSMs during anus-preserving surgeries (Chictr.org.cn No.: ChiCTR2300068991).

Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1.

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased NF-κB-dependent apoptosis specifically in tumors and not normal tissues, indicating that, in malignant cells, C5aR1 primarily regulated cell fate. Collectively, these data revealed that increased complement gene expression is part of the stress response mounted by irradiated tumors and that targeting C5aR1 could improve radiotherapy, even in tumors displaying immunosuppressive features.

Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancer.

Nanozyme-based catalytic therapy is an effective method for cancer treatment, but insufficient catalytic activity presents a challenge in achieving optimal therapeutic outcomes. External light can provide an innovative approach to modulate nanozyme catalytic activity. Herein, we report on plasmonic gold nanobipyramid@cuprous oxide (Au NBP@Cu2O) nanozyme for the effective phototherapy of breast cancer. In the tumor microenvironment, Cu+-mediated Fenton-like reaction catalyzes the generation of toxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide to induce apoptosis. Additionally, the Au NBP@Cu2O nanostructure improves the absorption performance of Au NBPs in the near-infrared II region through near-field enhancement of equipartite exciters and achieves a high photothermal conversion efficiency value of 58%. Remarkably, the Au NBP@Cu2O nanoheterostructure can capture hot electrons induced by equipartition excitations and promote electron-hole separation under 1064 nm laser irradiation, facilitating the production of more reactive oxygen species (ROS). The mechanism behind this enhanced catalytic activity was unraveled using femtosecond transient absorption spectroscopy. Both in vitro and in vivo investigations have demonstrated the efficacious tumor therapeutic potential of Au NBP@Cu2O nanozyme, particularly under 1064 nm laser irradiation. Furthermore, the proposed therapeutic approach has been proved to effectively block tumor metastasis, providing a promising strategy for the development of multifunctional nanotherapeutics to tackle metastatic tumors. STATEMENT OF SIGNIFICANCE: A highly effective plasmonic nanozyme has been developed to improve catalytic therapy for breast cancer. When exposed to 1064 nm laser irradiation, Au NBP@Cu2O nanozyme can promote the separation of hot electrons and holes thereby facilitating the production of reactive oxygen species. Hot electrons transfer behavior is unveiled by femtosecond transient absorption spectroscopy technique. This enhanced catalytic activity, along with the intrinsic photothermal effect, effectively kills tumor cells.

CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia.

Clinically, arsenic trioxide (ATO) was applied to the treatment of acute promyelocytic leukemia (APL) as a reliable and effective frontline drug. However, the administration regimen of AsⅢ was limited due to its fast clearance, short therapeutic window and toxicity as well. Based on CD71 overexpressed on APL cells, in present study, a transferrin (Tf)-modified liposome (LP) was established firstly to encapsulate AsⅢ in arsenic-nickel complex by nickel acetate gradient method. The AsⅢ-loaded liposomes (AsLP) exhibited the feature of acid-sensitive release in vitro. Tf-modified AsLP (Tf-AsLP) were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢ which stimulated reactive oxygen species level and caspase-3 activity. Tf-AsLP prolonged half-life of AsⅢ in blood circulation, lowered systemic toxicity, and promoted apoptosis and induced cell differentiation at lesion site in vivo. Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect, accordingly, a Tf-modified RA liposome (Tf-RALP) was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy. As expected, the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model. Furthermore, APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection. The effect of co-administration (Tf-AsLP + Tf-RALP) was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells' apoptosis and differentiation in peripheral blood and bone marrow. Collectively, Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug. Moreover, Tf-AsLP combined with Tf-RALP could achieve better efficacy. Thus, transferrin-modified AsⅢ liposome would be a novel clinical strategy to improve patient compliance, with promising translation prospects.

Nickel-Atom Doping as a Potential Means to Enhance the Photoluminescence Performance of Carbon Dots.

Heteroatom doping, particularly with nonmetallic atoms such as N, P, and S, has proven to be an effective strategy for modulating the fluorescent properties of carbon dots (CDs). However, there are few reports on the regulation of the photoluminescence of CDs by transition-metal doping. In this work, nickel-doped CDs (Ni-CDs) were fabricated using the hydrothermal approach. Ni atoms were incorporated into the sp2 domains of the CDs through Ni-N bonds, resulting in an increased degree of graphitization of the Ni-CDs. Additionally, Ni-atom doping served to shorten the electron transition and recombination lifetimes, and suppress the nonradiative recombination process, resulting in an absolute fluorescence quantum yield of 54.7% for the Ni-CDs. Meanwhile, the as-prepared Ni-CDs exhibited excellent biocompatibility and were utilized for fluorescent bioimaging of HeLa cells. Subsequently, the Ni-CDs were employed as fluorescent anticounterfeiting inks for the successful encryption of two-dimensional barcodes. Our work demonstrates a novel heteroatom doping strategy for the synthesis of highly fluorescence-emitting CDs.

[Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model].

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1ß and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1ß, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Recent Advances in Perfluorocarbon-Based Delivery Systems for Cancer Theranostics.

Hypoxia is a key impediment encountered in the treatment of most solid tumors, leading to immune escape and therapeutic resistance. Perfluorocarbons (PFCs) have a unique electrical structure and are characterized by a high solubility for gases. PFC-based oxygen carriers have been evaluated for their ability to deliver oxygen effectively to hypoxic tissues, and significant clinical translation has been demonstrated. And due to the unique acoustic activity, PFCs have been employed to stabilize the injection of gas microbubbles (MBs) as clinical ultrasonography contrast agents. In contrast, the ultrasound and photothermally activatable PFC phase-shift nanodroplets (P-SNDs) represent a novel alternative to ultrasound imaging and hypoxia improvement. The PFC-based oxygen carriers may be utilized to improve the efficacy of cancer treatments based on synergistic radiotherapy (RT), chemotherapy (CMT), and photodynamic therapy (PDT) to reshape the tumor microenvironment through synergistic immunotherapy (IMT) and to achieve precise tumor diagnosis using acoustic imaging. This review described the characteristics of PFCs to provide an update on the design of PFC delivery systems used for oxygen delivery and ultrasound imaging to facilitate the treatment and diagnosis of tumors. The objective was to contribute to overcoming the obstacles encountered during PFC research and provide the developing prospects.

Induce male sterility by CRISPR/Cas9-mediated mitochondrial genome editing in tobacco.

Genome editing has become more and more popular in animal and plant systems following the emergence of CRISPR/Cas9 technology. However, target sequence modification by CRISPR/Cas9 has not been reported in the plant mitochondrial genome, mtDNA. In plants, a type of male sterility known as cytoplasmic male sterility (CMS) has been associated with certain mitochondrial genes, but few genes have been confirmed by direct mitochondrial gene-targeted modifications. Here, the CMS-associated gene (mtatp9) in tobacco was cleaved using mitoCRISPR/Cas9 with a mitochondrial localization signal. The male-sterile mutant, with aborted stamens, exhibited only 70% of the mtDNA copy number of the wild type and exhibited an altered percentage of heteroplasmic mtatp9 alleles; otherwise, the seed setting rate of the mutant flowers was zero. Transcriptomic analyses showed that glycolysis, tricarboxylic acid cycle metabolism and the oxidative phosphorylation pathway, which are all related to aerobic respiration, were inhibited in stamens of the male-sterile gene-edited mutant. In addition, overexpression of the synonymous mutations dsmtatp9 could restore fertility to the male-sterile mutant. Our results strongly suggest that mutation of mtatp9 causes CMS and that mitoCRISPR/Cas9 can be used to modify the mitochondrial genome of plants.

Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway.

BACKGROUND: Parkinson's disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin exerts its protective effect on DAergic neurons remains unclear. PURPOSE: To investigate the underlying molecular mechanism of quercetin's protective effect on DA neurons using 1-methyl-4-phenylpyridinium (MPP+)-induced PD ferroptosis model in vitro. METHODS: MPP+ was used to induce cytotoxicity in SH-SY5Y/primary neurons. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The expression levels of ferroptosis-related proteins (NCOA4, SLC7A11, Nrf2, and GPX4) were determined by Western blotting. Malondialdehyde (MDA), iron, and GPX4 levels were assesed using corresponding assay kits. Lipid peroxidation was assessed by C11-BODIPY staining. RESULTS: In the MPP+-induced ferroptosis model of SH-SY5Y cells, the expressions of SLC7A11 and GPX4 were inhibited, and the expression of NCOA4 protein was increased, causing the overproduction of MDA and lipid peroxidation. Quercetin can reduce the above changes caused by MPP+, that is, reduce the protein expression of NCOA4 in SH-SY5Y cells, increase SLC7A11 and GPX4 partially inhibited by MPP+, and reduce MDA overproduction and lipid peroxidation to protect DA neurons. Nrf2 inhibitor ML385 could inhibit quercetin-induced increase of GPX4 and SLC7A11 protein expression, indicating that the protective effect of quercetin was mediated through Nrf2. CONCLUSIONS: The results of this study suggest that quercetin regulates ferroptosis through Nrf2-dependent signaling pathways, thereby inhibiting MPP+-induced neurotoxicity in SH-SY5Y/primary neurons.

Ultrasound-assisted carbon nanoparticle labeling of neoadjuvant chemotherapy for breast-conserving surgery in breast cancer.

Background: Neoadjuvant chemotherapy has gradually become an important means of breast cancer treatment; however, tumor regression following chemotherapy remains a concern. This study was conducted to investigate the effect of ultrasound-assisted carbon nanoparticle labeling in neoadjuvant chemotherapy for breast-conserving surgery in breast cancer. Methods: This was a prospective clinical trial study (clinical registration number: ChiCTR-OOC-15006844). Sixty-eight breast cancer patients confirmed by biopsy between July 2015 and January 2017 were randomly selected from the clinical data. Of these, 32 patients were screened for neoadjuvant chemotherapy, forming a consecutive, random series. An ultrasound-guided carbon nanotube was used to mark the original tumor, and sentinel lymph node biopsies were performed. After 4-6 cycles of standard neoadjuvant chemotherapy, 26 patients were selected for breast-conserving surgery. The feasibility and validity of carbon nanoparticle labeling were analyzed through the negative rate of incision margin, the volume of resected tumors, the detection rate of black-stained sentinel lymph nodes, the recurrence rate of ipsilateral breast, and postoperative survival. Results: In all, 32 patients underwent sentinel lymph node biopsy, 29 cases were detected (90.6%), the false-negative rate was 3.8% (1/26), and 0-4 sentinel lymph nodes (mean 1.8±1.1) were detected. A total of 26 patients underwent breast-conserving surgery, 5 underwent secondary excision, and 1 underwent subcutaneous adenectomy due to a positive margin. The minimum margin between the resected site and the infiltrated part was 1.0-2.1 cm (1.3±0.3 cm). The diameter of resected tumors ranged from 2.2 to 4.5 cm (3.1±0.6 cm). No recurrence or distant metastasis of ipsilateral breast tumors was observed during follow-up (the median follow-up time was 9 months). Conclusions: Ultrasound-assisted carbon nanoparticle labeling is effective for sentinel lymph node tracing before neoadjuvant chemotherapy and has a high detection rate for metastatic lymph nodes. During breast-conserving surgery, it can determine the extent of tumor resection to achieve precision surgical treatment.

Ratiometric fluorescent detection of exosomal piRNA-823 based on Au NCs/UiO-66-NH2 and target-triggered rolling circle amplification.

piR-823 is a newly discovered colorectal cancer marker with high diagnostic efficacy. However, the current quantification methods have complicated operations and high cost, which restrict its clinical application. Herein, a metal-organic framework (MOF) with a UiO-66 prototype structure which supports gold nanoclusters (Au NCs), Au NCs/UiO-66-NH2, were prepared as a model nanobiosensing platform for ratiometric detection of exosomal piR-823. The rolling circle amplification process provides high sensitivity and the ratiometric detection process ensures good accuracy of the sensor. Such biosensor showed a wide linear range of 0.04-4 pM, and a low detection limit of 10.2 fM towards piR-823. In addition, piR-823 can be used as an effective supplement to carcinoembryonic antigen (CEA) in clinical diagnosis of colorectal cancer. This study not only provides a potentially valuable ratio fluorescence platform involving enzyme catalytic reaction, but also offers a design blueprint for further expansion of nanotechnology in the diverse biological analysis.