Validating the 2023 FIGO staging system: A nomogram for endometrioid endometrial cancer and adenocarcinoma.

BACKGROUND: To find the factors impacting overall survival (OS) prognosis in patients with endometrioid endometrial carcinoma (EEC) and adenocarcinoma and to establish a nomogram model to validate the 2023 International Federation of Obstetrics and Gynecology (FIGO) staging system for endometrial cancer. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) training cohort. An independent validation cohort was obtained from the First Affiliated Hospital of Anhui Medical University between 2008 and 2023. Cox regression analysis identified independent prognostic factors for OS in EEC and adenocarcinoma patients. A nomogram predicting OS was developed and validated utilizing the C-index, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). The relationship between the tumor grade and prognosis of EEC and adenocarcinoma was quantified using net reclassification improvement (NRI), propensity score matching (PSM), and Kaplan-Meier curves. RESULTS: Cox regression analysis identified age, race, marital status, tumor grade, tumor stage, tumor size, and chemotherapy as independent prognostic factors for OS. A nomogram for predicting OS was developed based on these factors. The C-indexes for the OS nomogram was 0.743 and 0.720 for the SEER training set and external validation set, respectively. The area under the ROC (AUC) for the OS nomogram was 0.755, 0.757, and 0.741 for the SEER data subsets and 0.844, 0.719, and 0.743 for the external validation subsets. Calibration plots showed high concordance between the nomogram-predicted and observed OS. DCA also demonstrated the clinical utility of the OS nomogram. NRI, PSM, and survival analyses revealed that tumor grade was the most important histopathological factor for EEC and adenocarcinoma prognosis. CONCLUSION: Seven independent prognostic variables for the OS of patients with EEC and adenocarcinoma were identified. The established OS nomogram has good predictive ability and clinical utility and validates the 2023 endometrial cancer FIGO staging system.

CLCN3 in mediating the proliferation of human ovarian cancer cells.

Background: Chloride channel-3 (CLCN3), a crucial component of the voltage-gated chloride channel family, is implicated in numerous physiological and pathophysiological processes. This study aimed to investigate the characteristics of CLCN3 in pancancer and its influence on the immune response through the use of a range of databases. Concurrently, we assessed the impact of CLCN3 on the proliferation of ovarian cancer (OC) cells and explored its potential mechanisms. Methods: We employed the Tumor Immune Estimation Resource (TIMER) 2.0 and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to examine the messenger RNA (mRNA) and the protein expression of CLCN3 across various cancers. The prognostic significance of CLCN3 was evaluated using the Gene Expression Profiling Interactive Analysis 2.0 (GEPIA 2.0) database. The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) facilitated the analysis of CLCN3 promoter methylation levels. The association between CLCN3 expression and tumor-infiltrating immune cells was investigated using various algorithms. The cBioportal database facilitated the analysis of CLCN3 mutations and mutation sites across various cancers. The Tumor-Immune System Interactions Database (TISIDB) database was employed to explore the correlation between CLCN3 expression and immune or molecular subtypes across a variety of cancer types. We collected ovarian tissue samples, encompassing both normal ovarian and OC tissues. The human OC cell lines, SKOV3 cells and OVCAR433 cells, were cultured. CLCN3 expression was determined via reverse-transcription quantitative polymerase chain reaction (RT-qPCR), while phosphatidylinositol 3-kinase/Akt kinase (PI3K/AKT) expression was detected using Western blot. We utilized small interfering RNA (siRNA) technology to suppress CLCN3 expression. The proliferative capacity of SKOV3 and OVCAR433 cells was assessed using the Cell Counting Kit 8 (CCK-8) assay. Results: CLCN3 demonstrated an aberrant expression in a number of cancer types and was markedly reduced in OC tissues. Poor prognosis in cervical squamous cell cancer and myeloid leukemia was linked to excessive expression of CLCN3. The examination of immune cell infiltration, which included CD8+ T cells, B cells, T regulatory cells, and cancer-associated fibroblast cells, showed a strong association with aberrant CLCN3 expression. Following the use of siRNA technology, the ability of the ovarian carcinoma cell line SKOV3 and OVCAR433 to proliferate as well as the expression of PI3K/AKT both increased. Conclusions: CLCN3 is a possible biomarker for immune-related processes and the prognosis of cancer, and the PI3K/AKT signaling pathway may affect OC cells' ability to proliferate.

A sensitive immunosensor via Pd@Au0.85Pd0.15 in situ electrocatalysis generating H2O2 for quenching electrochemiluminescence of Ir(pbi)2(acac)@Ti3C2Tx MXene-PVA.

The establishment of rapid target analysis methods for cytokeratin fragment antigen 21-1 (CYFRA 21-1) is urgently needed. [Ir(pbi)2(acac)] (pbi = 2-(4-bromophenyl)-1-hydrogen -benzimidazole, acac = acetylacetonate) as traditional electrochemiluminescence (ECL) luminophores has been confined due to its non-negligible dark toxicity and poor water solubility leading to poor biocompatibility and electrical conductivity as an organic molecule. Hence, to overcome this limitation, [Ir(pbi)2(acac)] can be effectively loaded on the polyvinyl alcohol hydrogel modified Ti3C2Tx MXene surface (Ir@Ti3C2Tx-PVA) as sensing platform which can emit high ECL signals. Then, a quenching strategy was proposed to fabricate an ECL sandwich immunosensor using H2O2 as quencher molecules which can generated by Pd@Au0.85Pd0.15. Especially, the generation of O2 to H2O2 can be achieved through a two-electron (2e-) reaction pathway by Pd@Au0.85Pd0.15, to overcome the restriction that the H2O2 was virtually impossible to label or immobilize on the non-enzyme nanomaterials. The proposed ECL assay achieves a response to CYFRA 21-1 within the range of 0.1 pg/mL-100 ng/mL, with a detection limit of 8.9 fg/mL (S/N = 3). This work provided a feasible tactic to seek superior-performance ECL luminophore and quencher consequently set up a novel means to makeup ultrasensitive ECL biosensor, which extended the utilization potential of Ir(pbi)2(acac) in ECL assays.

An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models.

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.

LINC02532 by Mediating miR-541-3p/HMGA1 Axis Exerts a Tumor Promoter in Breast cancer.

The newly discovered LINC02532 is abnormally expressed in a variety of cancers and promotes cancer progression. The research proposed to discover the biological and molecular mechanisms of LINC02532 in breast cancer (BCa). In the resected BCa tissue samples and adjacent normal tissues, LINC02532, miR-541-3p, and High Mobility Group A1 (HMGA1) levels were determined. Cell function experiments were carried out on the premise of cell transfection with relevant plasmids. Based on that, the influence of LINC02532, miR-541-3p, and HMGA1 on MCF-7 cell activities (proliferation, migration, invasion, cell cycle, and apoptosis) was determined, as well as on EMT. Additionally, animal experiments were allowed to support cell experimental conclusions on LINC02532. Finally, the mechanistic network of LINC02532, miR-541-3p, and HMGA1 was identified. It was BCa tissues highly expressing LINC02532 and HMGA1, while lowly expressing miR-541-3p. Functionally, LINC02532 depletion repressed the activities and EMT process of MCF-7 cells. Silencing LINC02532 delayed tumor growth in mice. In terms of mechanism, LINC02532 mainly existed in the cytoplasm and could mediate HMGA1 expression by absorbing miR-541-3p. The findings offer new insights into the molecular mechanisms of LINC02532 in BCa and, more importantly, new strategies for the clinical treatment of BCa.

Electrochemiluminescence Sensor with Controlled-Release Triggering Electrostatic Attraction Elimination Mechanism for Trenbolone Trace Detection.

A controlled-release strategy can meet the needs of sensitive environmental monitoring for pollutants through a self-on/off mode. In this work, an electrochemiluminescence (ECL) biosensor with controlled-release triggering electrostatic attraction elimination and biomolecular stimulated response strategies was constructed to detect environmental steroid hormones sensitively. The blocked pores on the aminated mesoporous silica nanocontainers were opened by specific binding between the trenbolone (TB) antigen and the antibody. The released l-cysteine counteracted the negative charge on the MnO2 NF surface through the redox reaction between -SH and MnO2, making the electrostatic interaction between the MnO2 NFs and the Ru(dcbpy)32+ disappear. Ru(dcbpy)32+ released an ECL signal on the electrode, thus completing the controlled-release triggering electrostatic attraction elimination strategy. In addition, with the TB antibody as the target and the competition strategy between the TB antigen and the standard substance, the constructed controlled-release ECL biosensor was used to detect the TB standard substance. Moreover, MnO2 NFs as the substrate of the ECL biosensor increased the active specific surface area of the electrode, effectively catalyzing the production of OH• and O2•-, thus endowing the ECL biosensor with coreactant-catalytic enhancement characteristic and further improving its ECL performance. This sensitive signal response brought about a low limit of detection of 2.53 fg/mL for the constructed ECL biosensor, which contributed a feasible idea for efficient trace analysis of pollutants in the environment.

A photoelectrochemical sensor for Hg2+ detection with enhanced cathodic photocurrent via BiOI/Bi2S3 photoanode of self-sacrifice.

Due to the inherent merits of the anodic photoelectrochemical (PEC) sensor, it was widely utilized in the field of analytical chemistry. However, it must be noted that the anodic PEC sensor was susceptible to interference in practical applications. The situation with the cathodic PEC sensor was exactly the opposite. Therefore, this work fabricated a PEC sensor combining photoanode and photocathode that solved the defects of conventional PEC sensors in detecting Hg2+. Specifically, Na2S solution was carefully dropped on the BiOI-modified indium-tin oxide (ITO) to obtain ITO/BiOI/Bi2S3 directly by self-sacrifice method and the resulting electrode was used as photoanode. In addition, a sequential modification process was employed to decorate the ITO substrate with Au nanoparticles (Au NPs), Cu2O, and L-cysteine (L-cys), thereby realizing the fabrication of the photocathode. Moreover, the presence of Au NPs further amplified the photocurrent of the PEC platform. During the detection process, when Hg2+ is present it will bind to the L-cys, resulting in an increase in current, thus enabling sensitive detection of Hg2+. The proposed PEC platform exhibited good stability and reproducibility, providing a new idea for the detection of other heavy metal ions.

The tumor-stroma ratio and the immune microenvironment improve the prognostic prediction of pancreatic ductal adenocarcinoma.

Tumor-infiltrating immune cells and fibroblasts are significant components of the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), and they participate in tumor progression as closely as tumor cells. However, the relationship between the features of the TME and patient outcomes and the interactions among TME components are still unclear. In this study, we evaluated the PDAC TME in terms of the quantity and location of cluster of differentiation (CD)4+ T cells, CD8+ T cells, macrophages, stromal maturity, and tumor-stroma ratio (TSR), as evaluated by immunohistochemical staining of serial whole-tissue sections from 116 patients with PDAC. The density of T cells and macrophages (mainly activated macrophages) was significantly higher at the invasive margins (IMs) than at the tumor center (TC). CD4+ T cells were significantly association with all the other tumor-associated immune cells (TAIs) including CD8, CD68 and CD206 positive cells. Tumors of the non-mature (intermediate and immature) stroma type harbored significantly more CD8+ T cells at the IMs and more CD68+ macrophages at the IMs and the TC. The density of CD4+, CD8+, and CD206+ cells at the TC; CD206+ cells at the IMs; and tumor-node-metastasis (TNM) staging were independent risk factors for patient outcomes, and the c-index of the risk nomogram for predicting the survival probability based on the TME features and TNM staging was 0.772 (95% confidence interval: 0.713-0.832). PDAC harbored a significantly immunosuppressive TME, of which the IMs were the hot zones for TAIs, while cells at the TC were more predictive of prognosis. Our results indicated that the model based on the features of the TME and TNM staging could predict patient outcomes.

Chlorophenyl thiophene silicon phthalocyanine: Synthesis, two-photon bioimaging-guided lysosome target, and in vitro photodynamic efficacy.

The development of efficient photosensitizers with high singlet oxygen quantum yield, strong fluorescent emission, excellent photostability, and specific organelle targeting is in great demand for the enhancement of PDT treatment efficiency. This study designed and synthesized a new two-photon photosensitizer chlorophenyl thiophene axially substituted silicon (IV) phthalocyanine (CBT-SiPc). CBT-SiPc showed specific targeting of lysosomes in living cells and good biocompatibility. Furthermore, high 1O2 generation efficiency and high PDT efficiency in MCF-7 breast cancers under irradiation were also demonstrated. The novel CBT-SiPc showed great potential in the application of lysosome-targeted and two-photon bioimaging-guided photodynamic cancer therapy.

Morpholinyl silicon phthalocyanine nanoparticles with lysosome cell death and two-photon imaging functions for in vitro photodynamic therapy of cancer cells.

The lysosome is an important target for realizing antitumor therapy. Lysosomal cell death exerts significant therapeutic effects on apoptosis and drug-resistance. The development of lysosome-targeting nanoparticles to obtain efficient cancer treatment is challenging. In this article, nanoparticles composed of DSPE@M-SiPc and possessing bright two-photon fluorescence, lysosome targeting ability, and photodynamic therapy multifunctionalities are prepared by encapsulating morpholinyl-substituted silicon phthalocyanine (M-SiPc) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE). Two photon fluorescence bioimaging showed that M-SiPc and DSPE@M-SiPc mainly locate in lysosomes after cellular internalization. Upon irradiation, DSPE@M-SiPc effectively generates reactive oxygen species and damages the function of lysosome, subsequently leading to lysosomal cell death. DSPE@M-SiPc is a promising photosensitizer for cancer treatment.

Integrating Tetrathiafulvalene and Nickel-Bis(dithiolene) Units into Donor-Acceptor Covalent Organic Frameworks for Stable and Efficient Photothermal Conversion.

Tetrathiafulvalene (TTF) and Ni-bis(dithiolene) are typical conductive units widely studied in electronics, optics, and photochemistry. However, their applications in near-infrared (NIR) photothermal conversion are often limited by insufficient NIR absorption and low chemical/thermal stability. Herein, we integrate TTF and Ni-bis(dithiolene) into a covalent organic framework (COF) with stable and efficient NIR and solar photothermal conversion performance. Two isostructural COFs, namely Ni-TTF and TTF-TTF, are successfully isolated which are composed of TTF and Ni-bis(dithiolene) units as donor-acceptor (D-A) pairs or TTF units only. Both COFs show high BET surface areas and good chemical/thermal stability. Notably, compared with TTF-TTF, the periodic D-A arrangement in Ni-TTF significantly lowers the bandgap, leading to unprecedented NIR and solar photothermal conversion performance.

Comprehensive characterization of HER2-low breast cancers: implications in prognosis and treatment.

BACKGROUND: HER2-low cancers are heterogeneous with different degrees of HER2 expression and hormone receptor (HR) status. Currently, its analysis is mostly focused on the standard clinic-pathologic features or common biomarkers expression, without considering the heterogeneity within the category. A further characterization and understanding of this cancer subgroup will facilitate its management. METHODS: A large cohort of HER2-negative cancers (N = 1464) was included. The HER2-low (N = 412) and HER2-zero cancers (N = 1052) were compared and correlated with a comprehensive panel of clinico-pathologic features and biomarker expression according to different HER2 expressions and HR statuses. The prognostic values of these features in HER2-low cancers were also evaluated. FINDINGS: The characteristics of HER2-low breast cancers, as compared to HER2-zero, varied with the HR status. HER2-low luminal cancers were associated with younger age, larger tumor, high pAKT and high HLA expression. Among TNBCs, opposite trends in age and tumor size were found. Additionally, HER2-low TNBC showed less necrosis, higher pN, lower c-kit and CK14 than HER2-zero cancers. Nonetheless, regardless of HR status, HER2-low status was associated with increased COX2 and AR expression, implicated in the biology of HER2-low cancers. HER2-low cancers showed high expression of HLAs in tumors and PD-L1 in immune cells. In particular, the co-expression of HLAs was found to be associated with better survival in HER2-low cancers. INTERPRETATION: This study revealed further characteristic of HER2-low breast cancers as compared to HER2-zero cancers, provided further insights into its prognostication and therapeutic strategies. FUNDING: Health and Medical Research Fund (08190586), Cheng Yue Pui Charity Foundation and CUHK direct grant.

Controlled Growth of MoS2 on Dendritic Ferric Oxide to Enhance Electrochemiluminescence of Nitrogen-Doped Carbon Quantum Dots for Sensitive Immunoassay.

The essential expansion of electrochemiluminescence (ECL) technology into clinical detection relies on sensitive and stable signal and maintenance of the activity of the immune molecules during the analysis. This poses a critical challenge for an ECL biosensor as a luminophore in general requires high potential excitation resulting in a strong ECL signal; nevertheless, it has an irreversible effect on the activity of the antigen or antibody. Herein, a novel electrochemiluminescence (ECL) biosensor utilizing nitrogen-doped carbon quantum dots (N-CQDs) as emitters and molybdenum sulfide/ferric oxide (MoS2@Fe2O3) nanocomposites as a coreaction accelerator was developed for detection of neuron-specific enolase (NSE), a biomarker of small cell lung cancer. The doping of nitrogen allows the CQDs to exhibit ECL signals with low excitation potential, with a more viable activity possible for immune molecules. MoS2@Fe2O3 nanocomposites exhibit superior coreaction acceleration characteristics in hydrogen peroxide than any single component of them, and the highly branched dendrite microstructure provides a large number of binding sites for immune molecular, which is an inevitable factor for trace detection. In addition, ion beam sputtering gold particle technology is introduced into the sensor fabrication via an Au-N bond, which will provide sufficient density orientation for capturing the antibody load via the Au-N bonds. With excellent repeatability, stability, and specificity, the as-purposed sensing platform showed differentiated ECL responses of NSE range from 10.00 fg/mL to 500 ng/mL, and the limit of detection (LOD) was calculated of 6.30 fg/mL (S/N = 3). The proposed biosensor is prospective to provide a new avenue for the analysis of NSE or other biomarkers.

Bovine serum albumin-based and dual-responsive targeted hollow mesoporous silica nanoparticles for breast cancer therapy.

Combination therapy is an effective way to alleviate the shortcoming of monotherapy and enhances therapeutic efficacy. Herein, a distinctive hollow mesoporous silica nanoparticle (HMSNs) encapsulated with folic acid-modified bovine serum albumin (BSA-FA), denoted as HBF, was engineered for tumor targeting and dual-responsive release of loaded-therapeutic agents MD (methylene blue (MB) and doxorubicin (DOX)). The BSA molecule as a ''gatekeeper'' prevents premature drug leakage and actively unloads the cargos through BSA detachment in response to intracellular glutathione (GSH). Folic acid (FA) promotes the specific intracellular delivery of the drug to folate receptor (FR)-expressing cancer cells to improve the efficacy of chemo-photodynamic therapy (PDT). In vitro drug release profiles showed that the drug carrier could achieve pH/redox-responsive drug release from MD@HBF owing to the cleavage of the imine bonds between HMSNs-CHO and BSA-FA and BSA intramolecular disulfide bond. Additionally, a series of biological evaluations, such as cell uptake experiments, toxicity experiments, and in vivo therapeutic assays indicated that MD@HBF possesses the features of accurately targeting FR-expressing 4T1 cells to induce cells apoptosis in vitro, exhibits outstanding tumor cell synergistic killing efficiency of chemo-photodynamic therapy (combination index CI = 0.325), and inhibits tumors growth. These results demonstrated that the strategy of combining HMSNs with stimuli-responsive biodegradable protein molecules could provide a new potential direction toward the ''on-demand'' drug release for precision chemo-photodynamic therapy in cancer treatment.

Cu2O@PdAg-quenched CdS@CeO2 heterostructure electrochemiluminescence immunosensor for determination of prostate-specific antigen.

Based on the resonance energy transfer between CdS@CeO2 and Cu2O@PdAg, a quenching immunosensor for sensitive detection of prostate specific antigen (PSA) was constructed. The CdS@CeO2 heterostructure was obtained by in situ growth of CeO2 particles on the surface of CdS nanorods, and stable cathodic ECL emission was achieved using K2S2O8 as coreactant. Cu2O@PdAg was composed of Cu2O with tetradecahedral structure and bimetallic PdAg nanospheres and has a UV-V is absorption range between 600 and 800 nm. It overlaps with the ECL emission spectrum of CdS@CeO2, realizing the effective quenching of the ECL signal, which provides feasibility for subsequent practical application. The immunosensor exhibited good linearity in the concentration range 10 fg·mL-1 ~ 100 ng·mL-1, with a detection limit of 5.6 fg·mL-1. In sample analysis, the recoveries were 99.8-101%, and the relative standard deviation (RSD) was 0.85-1.6% showing great potential and development value for the sensitive detection of prostate cancer.

Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials.

Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O2 by a photosensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.

Ultrasensitive Electrochemiluminescence Biosensor with Silver Nanoclusters as a Novel Signal Probe and α-Fe2O3-Pt as an Efficient Co-reaction Accelerator for Procalcitonin Immunoassay.

Herein, a high-efficiency biosensor based on ternary electrochemiluminescence (ECL) system was constructed for procalcitonin (PCT) detection. Specifically, silver nanoclusters (Ag NCs) with stable luminescence properties were prepared with small-molecule lipoic acid (LA) as the ligand, and its ECL emission in persulfate (S2O82-) was first reported. Meanwhile, the prepared Ag NCs possessed ligand-to-metal charge-transfer characteristics, thus transferring energy from LA to Ag+ for luminescence. Based on the small particle size, good biocompatibility, and molecular binding ability, Ag NCs-LA was used as an ideal luminescent probe. In addition, α-Fe2O3-Pt was introduced to facilitate the activation of S2O82-, thereby generating more sulfate radicals to react with the free radicals of Ag NCs to enhance ECL emission. The synergistic effect of the variable valence state of transition metals and high catalytic activity of noble metals endows α-Fe2O3-Pt with excellent catalytic ability for S2O82-. Importantly, the sensing mechanism was systematically demonstrated by UV-vis, fluorescence, and ECL analysis, as well as density functional theory calculations. At last, NKFRGKYKC was designed for specific immobilization of antibodies, thus releasing the antigen binding sites to improve the antigen recognition efficiency. Based on this, the developed biosensor showed high sensitivity for PCT detection, with a wide linear range (10 fg/mL-100 ng/mL) and a low detection limit (3.56 fg/mL), which could be extended to clinical detection of multiple biomarkers.

PB@PDA nanocomposites as nanolabels and signal reporters for separate-type cathodic photoelectrochemical immunosensors in the detection of carcinoembryonic antigens.

Photoelectrochemical (PEC) immunoassays exhibiting high sensitivity and decent operability have considerable potential in areas such as cancer diagnostics. In particular, cathodic PEC configurations can prevent interference from reductive substances, which can occur in biological samples; however, challenges remain in terms of sensitivity and operability. In this study, separate-type PEC immunoassays were developed for carcinoembryonic antigen (CEA) by combining microplate-based immune recognition and off-on cathodic PEC detection. Polydopamine (PDA)-coated Prussian blue (PB) nanoparticles (PB@PDA NPs) were used as signal tags to label the detection antibody. The PB NPs and PDA captured on the microplates both disassembled under strongly alkaline conditions to generate redox-active electron acceptors. The disassembled products were quantitatively transferred to PEC detection cells and synergistically enhanced the PEC current with microstructured BiOI, which operated as a cathodic semiconductor electrode. As proof of principle, carcinoembryonic antigen (CEA) was applied to elucidate the potential application of PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was 0.001-100 ng mL-1 with the detection limit of 54.9 fg mL-1 (S/N = 3). The proposed separate-type off-on PEC strategy showed high sensitivity and decent operability for CEA detection, indicating its potential for the identification of other tumor markers.