Biomimetic Cancer-Targeting Nanoplatform Boosting AIEgens-Based Photodynamic Therapy and Ferroptosis by Disrupting Redox-Homeostasis.

Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSADSP@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.

Exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of hepatocellular carcinoma by inhibiting HIPK3.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with rich blood supply. HCC-derived exosomes containing hereditary substances including microRNAs (miRNAs) were involved in regulating tumor angiogenesis and metastasis. Subsequently, series experiments were performed to evaluate the effect of exosomal miR-3174 on HCC angiogenesis and metastasis. HCC-derived exosomal miR-3174 was ingested by human umbilical vein endothelial cells (HUVECs) in which HIPK3 was targeted and silenced, causing subsequent inhibition of Fas and p53 signaling pathways. Furthermore, exosomal miR-3174 induced permeability and angiogenesis of HUVECs to enhance HCC progression and metastasis. Under hypoxia, upregulated HIF-1α further promoted the transcription of miR-3174. Moreover, HNRNPA1 augmented the package of miR-3174 into exosomes. Clinical data analysis confirmed that HCC patients with high-level miR-3174 were correlated with worse prognosis. Thus, exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of HCC by inhibiting HIPK3/p53 and HIPK3/Fas signaling pathways. Our findings might provide potential targets for anti-tumor therapy.

Fluorinated Cell-Penetrating Peptide for Co-Delivering siHIF-1α and Sorafenib to Enhance In Vitro Anti-Tumor Efficacy.

Antiangiogenic therapy with sorafenib (SF) alone is ineffective in eradicating tumors, and its long-term application can exacerbate tumor hypoxia, which in turn restricts SF's therapeutic efficacy. Here, a redox-responsive fluorinated peptide (DEN-TAT-PFC) consisting of dendritic poly-lysine, cell-penetrating peptide TAT, and perfluorocarbon was designed and synthesized to co-load siRNA-targeting hypoxia-inducible factors (siHIF-1α) and SF. The unique architecture of the peptide and fluorinated modifications enhanced the siRNA delivery efficiency, including increased siRNA binding, GSH-responsive release, cellular uptake, endosomal escape, and serum resistance. Simultaneously, the DEN-TAT-PFC/SF/siHIF-1α co-delivery system achieved efficient knockdown of HIF-1α at mRNA and protein levels, thus alleviating hypoxia and further substantially reducing VEGF expression. Additionally, the excellent oxygen-carrying ability of DEN-TAT-PFC may facilitate relief of the hypoxic microenvironment. As a result of these synergistic effects, DEN-TAT-PFC/SF/siHIF-1α exhibited considerable anti-tumor cell proliferation and anti-angiogenesis effects. Therefore, DEN-TAT-PFC can be a versatile platform for fabricating fluorine-containing drugs/siRNA complex nano-systems.

Molecular Charge and Antibacterial Performance Relationships of Aggregation-Induced Emission Photosensitizers.

Bacterial infections remain a major cause of morbidity worldwide due to drug resistance of pathogenic bacteria. Photodynamic therapy (PDT) has emerged as a promising approach to overcome this drug resistance. However, existing photosensitizers (PSs) are broad-spectrum antibacterial agents that dysregulate the microflora balance resulting in undesirable side effects. Herein, we synthesized a series of aggregation-induced emission (AIE)-active PSs with a lipophilic cationic AIE core with varying charges, named TBTCP and its derivatives. The association of the difference in their molecular charge with the antibacterial effects was systemically investigated. Among the derivatives presented, TBTCP-SF with the electronegative sulfonate group nulled its ability to bind to and ablate Gram-positive (G+) or Gram-negative (G-) bacteria. TBTCP-QY modified by electropositive quaternary ammonium facilitated binding and augmented the photodynamic antibacterial activity for both G+ and G- bacteria. TBTCP-PEG with hydrophilic neutral ligands selectively bound and inactivated G+ bacteria. Under white-light illumination, TBTCP-PEG ablated 99.9% methicillin-resistant Staphylococcus aureus (MRSA) and promoted wound healing in MRSA-infected mice, eliminating MRSA infection both in vitro and in vivo. Our work provides unprecedented insight into the utility of AIE-active PSs for highly targeted and efficient photodynamic ablation of either G+ or G- bacteria that can be translated to next-generation antibacterial materials.

A human VEGF magnetic molecularly imprinted polymer for drug-free anti-angiogenesis and photothermal therapy of tumors.

A magnetic molecularly imprinted polymer was developed with an epitope peptide of human VEGF as a template via an epitope blotting technique. As a drug-free agent, the nanoparticles can significantly suppress the proliferation of tumor cells by integrating anti-angiogenesis and photothermotherapy. This work provides a successful example of the design of multimodal antineoplastic drugs.

Supporting nanoscale zero-valent iron onto shrimp shell-derived N-doped biochar to boost its reactivity and electron utilization for selenite sequestration.

Nanoscale zero-valent iron (nZVI) has been widely used in the reductive removal of contaminants from water, yet it still fights against the inherent passive cover and the raise of medium pH. In this study, nZVI was supported onto a nitrogen-doped biochar (NBC) that was prepared by pyrolyzing shrimp shell for efficiently sequestrating aqueous selenite (Se(IV)). The resultant composite (NBC-nZVI) revealed a higher reactivity and electron utilization efficiency (EUE) than the bare nZVI in Se(IV) sequestration because of the positive charge, the buffering effect and the good conductivity of NBC. The kinetic rate and EUE of NBC-nZVI were increased by 143.4% and 15.3% compared to the bare nZVI, respectively, at initial pH of 3.0. The high removal capacity of 605.4 mg g-1 for NBC-nZVI was obtained at Se(IV) concentration of 1000 mg L-1, initial pH of 3.0, NBC-nZVI dosage of 1.0 g L-1 and contact time of 12 h. Moreover, NBC-nZVI exhibited a strong tolerance to solution pHs and coexisting compounds (e.g., humic acid) and could reduce the Se(IV) concentration from 5.0 mg L-1 to below the limit of drinking water (50 µg L-1) in real-world samples. This work exemplified a utilization of shrimp shell-derived NBC to simultaneously enhance the reactivity and EUE of nZVI for reductively removing contaminants.

The locoregional adiponectin and its synergistic antitumor effect with HIF-1α blockade in TSCC.

Adiponectin (APN) is a kind of endogenous anti-tumor adipocytokine, which exerts its function by binding to its receptors (AdipoR1 and AdipoR2). However, hyperadiponectinemia is found in some pathophysiological processes without significant protective effect, which indicates the existence of APN resistance. Here, we aimed to investigate the locoregional expression of APN in tongue squamous cell carcinoma (TSCC) tissues, and to explore the potential regulatory mechanism of APN resistance under hypoxia. Consequently, we found that the protein expression of APN and AdipoR1, but not AdipoR2, was upregulated in the early stage of TSCC and after hypoxic treatment ex vivo and in vitro. Knockdown of HIF-1α decreased the level of APN and AdipoR1, and simultaneously, HIF-1α was identified as transcriptor of the APN. Intriguingly, a regenerative feedback of HIF-1α was unexpectedly detected after application of recombinant globular APN (gAPN), which most likely contributed to the APN resistance. Furthermore, HIF-1α blockade combined with gAPN has a prominent synergistic antitumor effect, which suggested an effective amelioration in APN resistance. In all, our study revealed the possible mechanism of APN resistance under hypoxia and provides a promising strategy of bi-target treatment with APN and HIF-1α for TSCC therapy.

Synergistically Enhancing Tumor Chemotherapy Using an Aggregation-Induced Emission Photosensitizer on Covalently Conjugated Molecularly Imprinted Polymer Nanoparticles.

Due to the polygenic and heterogeneous nature of the tumorigenesis process, traditional chemotherapy is far from desirable. Fabricating multifunctional nanoplatforms integrating photodynamic effect can synergistically enhance chemotherapy because they can make the cancer cells much sensitive to chemotherapeutics. However, how to assemble different units in nanoplatforms and minimize side effects caused by chemodrugs and photosensitizers (PSs) still needs to be explored. Herein, a nanoplatform CPP/PS-MIP@DOX is developed using a simultaneously covalently conjugated new aggregation-induced emission (AIE) PS and a cell-penetrating peptide (CPP) on the surface of silica-based molecularly imprinted polymer (MIP) nanoparticles, prepared with doxorubicin (DOX) as the template in the water system via a sol-gel technique. CPP/PS-MIP@DOX has good biocompatibility, high DOX-loading ability, promoted cellular uptake, and sustained and pH-sensitive drug release capability. Furthermore, it can efficiently penetrate into tumor tissue, accurately home to, and accumulate at the tumor site. As a result, a better efficacy with lower cytotoxicity is achieved with a smaller dosage of DOX by utilizing either the photodynamic effect or unique characteristics of the MIP. It is the first nanoplatform fabricated by chemically conjugating AIE PSs directly on the surface of the scaffold via the surface-decorated strategy and successfully applied in cancer therapy. This work provides an effective strategy by constructing AIE PS-based cancer nanomedicines with MIPs as scaffolds.

Identification of lipid metabolism-associated genes as prognostic biomarkers based on the immune microenvironment in hepatocellular carcinoma.

Lipid metabolism has been associated with progression of various cancers. However, the underlying mechanisms of the impact of lipid metabolism-associated genes (LMAGs) on the tumor immune microenvironment have not been well-elucidated. This study aimed to determine the effects of lipid metabolism on the progression and development of hepatocellular carcinoma (HCC). Expression profiles and clinical data of 371 and 231 patients with HCC were obtained from the TCGA and Internal Cancer Genome Consortium (ICGC) databases, respectively. Using Cox regression and LASSO regression analyses, a prognostic risk model was constructed based on the LMAG data. The tumor mutation burden (TMB), immune cell infiltration levels, and immune response checkpoints of the identified risk groups were determined and compared. A total of two clusters were identified based on the LMAG expression, showing significant differences in tumor stage and immune cell infiltration. A prognostic risk model based on four LMAGs was constructed and proven to have a significant prognostic value. The 1-, 3-, and 5-year survival rates in the high-risk group were 62.2%, 20.5%, and 8.1%, respectively, whereas those in the low-risk group were 78.9%, 28.1%, and 13.5%, respectively. The survival differences between the two risk groups were likely associated with TP53 mutation status, TMB score, degree of immunocyte infiltration, and immune checkpoint level. Likewise, the expression level of every LMAG included in the model had the same effect on the overall survival and immune cell infiltration levels. More importantly, the prognostic value of the signature was verified in an independent ICGC cohort. Thus, the expression levels of LMAGs are closely related to the tumor microenvironment in HCC and may serve as promising biological indicators for prognosis and immune therapy in patients with HCC.

Machine Learning to Improve Prognosis Prediction of Early Hepatocellular Carcinoma After Surgical Resection.

BACKGROUND: Improved prognostic prediction is needed to stratify patients with early hepatocellular carcinoma (EHCC) to refine selection of adjuvant therapy. We aimed to develop a machine learning (ML)-based model to predict survival after liver resection for EHCC based on readily available clinical data. METHODS: We analyzed data of surgically resected EHCC (tumor≤5 cm without evidence of extrahepatic disease or major vascular invasion) patients from the Surveillance, Epidemiology, and End Results (SEER) Program to train and internally validate a gradient-boosting ML model to predict disease-specific survival (DSS). We externally tested the ML model using data from 2 Chinese institutions. Patients treated with resection were matched by propensity score to those treated with transplantation in the SEER-Medicare database. RESULTS: A total of 2778 EHCC patients treated with resection were enrolled, divided into 1899 for training/validation (SEER) and 879 for test (Chinese). The ML model consisted of 8 covariates (age, race, alpha-fetoprotein, tumor size, multifocality, vascular invasion, histological grade and fibrosis score) and predicted DSS with C-Statistics >0.72, better than proposed staging systems across study cohorts. The ML model could stratify 10-year DSS ranging from 70% in low-risk subset to 5% in high-risk subset. Compared with low-risk subset, no remarkable survival benefits were observed in EHCC patients receiving transplantation before and after propensity score matching. CONCLUSION: An ML model trained on a large-scale dataset has good predictive performance at individual scale. Such a model is readily integrated into clinical practice and will be valuable in discussing treatment strategies.

The Anti-Tumor Mechanism and Target of Triptolide Based on Network Pharmacology and Molecular Docking.

BACKGROUND: According to the special physiological and pharmacological activities of natural compounds, many drugs with special therapeutic effects have been developed. The Triptolide (TP) is a natural anti-tumor drug with a world patent, but its target and mechanism are yet unknown. OBJECTIVE: The study aims to explore and predict the target and mechanism of TP on Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PC) and Colorectal Cancer (CC) through network pharmacology technology. METHODS: We screened the core targets of TP with NSCLC, PC and CC, respectively, and carried out network analysis, enrichment analysis and ligand-receptor docking to clarify its potential pharmacological mechanism. RESULTS: By screening the core genes between TP with NSCLC, PC and CC, respectively, it was found that PTGS2 was the common target gene in the three cancers. NSCLC, CCL2, IL6, HMOX1 and COL1A1 are the specific target genes, while MMP2, JUN, and CXCL8 are the specific target genes in PC. In CC, the specific target genes includeERBB2, VEGFA, STAT1 and MAPK8. In enrichment analysis, it was found that the NF- κB, toll-like receptors and IL-17 signaling pathway were mainly involved in TP for these cancers. The binding energy of TP to the core target is less than that of cyclophosphamide. CONCLUSION: This study preliminarily revealed that TP may prevent and treat cancers\ through multiple targets and pathways. The possible mechanisms of TP include regulating immune and inflammatory responses, promoting apoptosis and inhibiting tumor development. It shows that TP may have potential in treating kinds of tumors.

Simple synthesis of multifunctional photosensitizers for mitochondrial and bacterial imaging and photodynamic anticancer and antibacterial therapy.

Photosensitizers (PSs), a critical drug administered for successful photodynamic therapy (PDT), have been well researched regarding their anticancer or bactericidal capability with high precision and low invasiveness. Although traditional PSs have been explored either in photodynamic anticancer or in antibiosis, they usually require synthesis with multiple steps, harsh synthetic conditions, and a complicated purification process for a single targeted product. Therefore, developing new multifunctional PSs with a simple synthesis and reactant flexibility which combine mitochondrial and bacterial imaging, efficient photodynamic anticancer and antibacterial effects is of the utmost urgency and of great importance for clinical applications. Herein, a large structural investigation of isoquinolinium-based PSs synthesized by a simple Rh-catalysed annulation reaction with high yields is presented. These lipophilic cationic PSs have a tunable photophysical property. LIQ-6 was found to perform not only as an ideal mitochondria targeting probe but also an effective cancer cell killing PS, and moreover, a tracker for bacterial imaging and ablation. LIQ-6 can be used to image a wide range of cancer cells and to monitor the photo-induced cell apoptosis, and simultaneously, it can also image and be a photodynamic germicide for both Gram-positive and Gram-negative bacteria. Furthermore, LIQ-6 shows great effectiveness in the wound healing process, showing its ability to be an ideal PS in vivo as well. This contribution is believed to offer a new platform for the construction of a theragnostic system for future practical applications in biology and biomedicine.

Development and Validation of Pre- and Post-Operative Models to Predict Recurrence After Resection of Solitary Hepatocellular Carcinoma: A Multi-Institutional Study.

BACKGROUND: The ideal candidates for resection are patients with solitary hepatocellular carcinoma (HCC); however, postoperative recurrence rate remains high. We aimed to establish prognostic models to predict HCC recurrence based on readily accessible clinical parameters and multi-institutional databases. PATIENTS AND METHODS: A total of 485 patients undergoing curative resection for solitary HCC were recruited from two independent institutions and the Cancer Imaging Archive database. We randomly divided the patients into training (n=323) and validation cohorts (n=162). Two models were developed: one using pre-operative and one using pre- and post-operative parameters. Performance of the models was compared with staging systems. RESULTS: Using multivariable analysis, albumin-bilirubin grade, serum alpha-fetoprotein and tumor size were selected into the pre-operative model; albumin-bilirubin grade, serum alpha-fetoprotein, tumor size, microvascular invasion and cirrhosis were selected into the postoperative model. The two models exhibited better discriminative ability (concordance index: 0.673-0.728) and lower prediction error (integrated Brier score: 0.169-0.188) than currently used staging systems for predicting recurrence in both cohorts. Both models stratified patients into low- and high-risk subgroups of recurrence with distinct recurrence patterns. CONCLUSION: The two models with corresponding user-friendly calculators are useful tools to predict recurrence before and after resection that may facilitate individualized management of solitary HCC.

Depletion of NK cells attenuates paraquat-induced acute lung injury by manipulating macrophage polarization.

Acute lung injury is the main causative factor in paraquat dichloride (PQ)-induced mortality. The innate immune system-triggered detrimental inflammatory cascade plays a vital role in PQ-induced acute lung injury. However, the role of natural killer (NK) cells, which are essential for innate response, in PQ-induced acute lung injury remains largely unknown. Here, we found that in an acute PQ poisoning model, depletion of NK cells attenuated PQ-induced lung injury by inhibiting macrophage polarization towards the M1 type. Specifically, the percentages of NK cells were reduced in the lung, spleen, and peripheral blood in a murine model of acute PQ poisoning. NK cells were aberrantly activated, evidenced by upregulation of the activating markers CD69, CD107a, and NKG2D and downregulation of the inhibitive marker KLRG1. Further, NK-specific depletion in mice greatly prolonged the survival time and ameliorated reactive oxygen species-induced damage following PQ treatment compared with the control group. Importantly, NK cell depletion alleviated macrophage and neutrophil infiltration in the lung and reversed PQ induced-macrophage polarization towards the pro-inflammatory M1 type. Our study demonstrates a crucial role of NK cells and NK cell-to-macrophage interaction in PQ-induced acute lung injury.

A Small-Molecule AIE Chromosome Periphery Probe for Cytogenetic Studies.

The chromosome periphery (CP) is a complex network that covers the outer surface of chromosomes. It acts as a carrier of nucleolar components, helps maintain chromosome structure, and plays an important role in mitosis. Current methods for fluorescence imaging of CP largely rely on immunostaining. We herein report a small-molecule fluorescent probe, ID-IQ, which possesses aggregation-induced emission (AIE) property, for CP imaging. By labelling the CP, ID-IQ sharply highlighted the chromosome boundaries, which enabled rapid segmentation of touching and overlapping chromosomes, direct identification of the centromere, and clear visualization of chromosome morphology. ID-IQ staining was also compatible with fluorescence in situ hybridization and could assist the precise location of the gene in designated chromosome. Altogether, this study provides a versatile cytogenetic tool for improved chromosome analysis, which greatly benefits the clinical diagnostic testing and genomic research.

Radiomic Features at Contrast-enhanced CT Predict Recurrence in Early Stage Hepatocellular Carcinoma: A Multi-Institutional Study.

Background Early stage hepatocellular carcinoma (HCC) is the ideal candidate for resection in patients with preserved liver function; however, cancer will recur in half of these patients and no reliable prognostic tool has been established. Purpose To investigate the effectiveness of radiomic features in predicting tumor recurrence after resection of early stage HCC. Materials and Methods In total, 295 patients (median age, 58 years; interquartile range, 50-65 years; 221 men) who underwent contrast material-enhanced CT and curative resection for early stage HCC that met the Milan criteria between February 2009 and December 2016 were retrospectively recruited from three independent institutions. Follow-up consisted of serum α-fetoprotein level, liver function tests, and dynamic imaging examinations every 3 months during the first 2 years and then every 6 months thereafter. In the development cohort of 177 patients from institution 1, recurrence-related radiomic features were computationally extracted from the tumor and its periphery and a radiomics signature was built with least absolute shrinkage and selection operator regression. Two models, one integrating preoperative and one integrating pre- and postoperative variables, were created by using multivariable Cox regression analysis. An independent external cohort of 118 patients from institutions 2 and 3 was used to validate the proposed models. Results The preoperative model integrated radiomics signature with serum α-fetoprotein level and tumor number; the postoperative model incorporated microvascular invasion and satellite nodules into the above-mentioned predictors. In both study cohorts, two radiomics-based models provided better predictive performance (concordance index ≥0.77, P < .05 for all), lower prediction error (integrated Brier score ≤0.14), and larger net benefits, as determined by means of decision curve analysis, than rival models without radiomics and widely adopted staging systems. The radiomics-based models gave three risk strata with high, intermediate, or low risk of recurrence and distinct profiles of recurrent tumor number. Conclusion The proposed radiomics models with pre- and postresection features helped predict tumor recurrence for early stage hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article.

Preparation of porous magnetic molecularly imprinted polymers for fast and specifically extracting trace norfloxacin residue in pork liver.

Here, magnetic molecularly imprinted polymers were designed for norfloxacin via oil-in-water emulsifier-free emulsion method. It was prepared by simply mixing norfloxacin, methacrylic acid-co-ethylene glycol dimethacrylate copolymer, and Fe3 O4 together at room temperature. Characterized by multiple analytical tools, the particle size, pore size, pore volume, specific surface area, and saturation magnetization of the product were about 30 µm, 10-500 nm, 2.92 mL/g, 105.84 m2 /g, and 3.052 emu/g, respectively. And the adsorption capacity was high at 27.04 mg/g towards norfloxacin. Combined with ultra high performance liquid chromatography, it was used to determine norfloxacin in real samples. Average recoveries were above 77.44% with relative standard deviations between 1.21 and 6.85% at three spiked levels (n = 3) for lake water and pork liver. The determination was achieved for the most complex biosample pork liver spiked with norfloxacin low to 30 ng/g, about 100 times less than the maximum residue limit regulated by Commission of the European Communities. All evidences demonstrated that the magnetic molecularly imprinted polymers can be used in practice for monitoring norfloxacin either in environmental water or meat product with high accuracy and reliability.

Machine-learning analysis of contrast-enhanced CT radiomics predicts recurrence of hepatocellular carcinoma after resection: A multi-institutional study.

BACKGROUND: Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence. METHODS: A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3. FINDINGS: Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633-0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733-0.801 and integrated Brier score of 0.147-0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns. INTERPRETATION: When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.

Ultrafast labeling and high-fidelity imaging of mitochondria in cancer cells using an aggregation-enhanced emission fluorescent probe.

An aggregation-enhanced emission mitochondrial probe, LIQ-3, was developed for ultrafast labeling within one minute and for distinguishing cancer cells from normal cells. Furthermore, the probe revealed high-fidelity tracking of mitochondria in a three-dimensional localization with advantages that include a specific targeting capacity and a high signal-to-noise ratio.

A near-infrared biothiol-specific fluorescent probe for cancer cell recognition.

Cancer is a global health issue and a leading cause of death. The discrimination of cancer cells from normal cells is of significant importance for the early diagnosis of cancers. As one of the useful biomarkers for developing cancer diagnosis and chemotherapy resistance systems, biothiols not only play an essential role in physiological and pathological processes but also exhibit cytoprotective effects in the susceptibility to carcinogenesis. It would be highly desirable to explore near-infrared biothiol-specific fluorescent probes for cancer diagnosis with outstanding specificity. In this study, a novel near-infrared fluorescent probe BPO-THAZ decorated with thiazole as a recognition site was presented for sensitive and selective detection of endogenous biothiols. BPO-THAZ can be used to not only evaluate the biothiol level in living HeLa cells upon treatment with H2O2 or anti-cancer drugs but also assess endogenous biothiols in stem cells. Furthermore, BPO-THAZ was successfully utilized to discriminate cancer cells from normal cells showing great promise for cancer diagnosis.