Search

To avoid the unexpected aggregation and reduce the cytotoxicity of nanomaterials as optical probes in cell imaging applications, we propose a programmed DNA-cube as a carrier for silver nanoparticles (Ag NPs) to construct a specific hydrogen sulfide (H2S) responsive platform (Ag NP@DNA-cube) for diagnosing colorectal cancer (CRC) in this study. The DNA-cube maintains good dispersion of Ag NPs while providing excellent biocompatibility. Based on the characteristic overexpression of endogenous H2S in CRC cells, the Ag NPs are etched by H2S within target cells into silver sulfide quantum dots, thereby selectively illuminating the target cells. The Ag NP@DNA-cube exhibits a specific fluorescence response to CRC cells and achieves satisfactory imaging. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer. [ABSTRACT FROM AUTHOR]

Biologically‐active near‐ultraviolet emitting spirooxindole‐pyrrolidine/pyrrolothiazole‐β‐ketothiolester have been synthesised via Chemo‐/regio‐/stereoselective manner. Excited‐state intramolecular proton transfer (ESIPT) of β‐ketothiolester exhibits excitation‐dependent emission with intermolecular hydrogen bonding ability with solvents. The emission could be tunable between 330 nm to 460 nm. Selected fluorescent compounds 4{4,2,1}, 4{12,2,2}, 5{4,2,1} and 5{12,2,2} shows cytotoxicity effect on PC3 cells, where the highest IC50 value (6 μM) was found for the probe 5{12,2,2}. The fluorescent behavior of 5{4,2,1} and 5{12,2,2} acted as an imaging molecule against cancer cells. [ABSTRACT FROM AUTHOR]

Fluorescent graphitic carbon nitride (g-C3N4) doped with various heteroatoms, such as B, P, and S, named Bg-C3N4, Pg-C3N4, and Sg-C3N4, were synthesized with variable band-gap values as diagnostic materials. Furthermore, they were embedded within hyaluronic acid (HA) microgels as g-C3N4@HA microgel composites. The g-C3N4@HA microgels had a 0.5–20 μm size range that is suitable for intravenous administration. Bare g-C3N4 showed excellent fluorescence ability with 360 nm excitation wavelength and 410–460 emission wavelengths for possible cell imaging application of g-C3N4@HA microgel composites as diagnostic agents. The g-C3N4@HA-based microgels were non-hemolytic, and no clotting effects on blood cells or cell toxicity on fibroblasts were observed at 1000 μg/mL concentration. In addition, approximately 70% cell viability for SKMEL-30 melanoma cells was seen with Sg-C3N4 and its HA microgel composites. The prepared g-C3N4@HA and Sg-C3N4@HA microgels were used in cell imaging because of their excellent penetration capability for healthy fibroblasts. Furthermore, g-C3N4-based materials did not interact with malignant cells, but their HA microgel composites had significant penetration capability linked to the binding function of HA with the cancerous cells. Flow cytometry analysis revealed that g-C3N4 and g-C3N4@HA microgel composites did not interfere with the viability of healthy fibroblast cells and provided fluorescence imaging without any staining while significantly decreasing the viability of cancerous cells. Overall, heteroatom-doped g-C3N4@HA microgel composites, especially Sg-C3N4@HA microgels, can be safely used as multifunctional theragnostic agents for both diagnostic as well as target and treatment purposes in cancer therapy because of their fluorescent nature. [ABSTRACT FROM AUTHOR]

The immune system has evolved to detect foreign antigens and deliver coordinated responses, while minimizing "friendly fire." Until recently, studies investigating the behavior of immune cells were limited to static in vitro measurements. Although static measurements allow for real-time imaging, results are often difficult to translate to an in vivo setting. Multiphoton microscopy is an emerging method to capture spatial information on subcellular events and characterize the local microenvironment. Previous studies have shown that multiphoton microscopy can monitor changes in single-cell macrophage heterogeneity during differentiation. Therefore, there is a need to use multiphoton microscopy to monitor molecular interactions during immunological activities like phagocytosis. Here we investigate the correlation between phagocytic function and changes in endogenous optical reporters during phagocytosis. In vitro autofluorescence imaging of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) was used to detect metabolic changes in macrophages during phagocytosis. More specifically, optical redox ratio, mean NADH fluorescence lifetime and ratio of free to protein-bound NADH were used to quantify changes in metabolism. Results show that IFN-γ (M1) macrophages showed decreased optical redox ratios and mean NADH lifetime while phagocytosing immunogenic cancer cells compared to metastatic cells. To validate phagocytic function, a fluorescence microscopy-based protocol using a pH-sensitive fluorescent probe was used. Results indicate that M0 and M1 macrophages show similar trends in phagocytic potential. Overall, this work demonstrates that in vitro multiphoton imaging can be used to longitudinally track changes in phagocytosis and endogenous metabolic cofactors. [ABSTRACT FROM AUTHOR]

As an important barrier between the cytoplasm and the microenvironment of the cell, the cell membrane is essential for the maintenance of normal cellular physiological activities. An abnormal cell membrane is a crucial symbol of body dysfunction and the occurrence of variant diseases; therefore, the visualization and monitoring of biomolecules associated with cell membranes and disease markers are of utmost importance in revealing the biological functions of cell membranes. Due to their biocompatibility, programmability, and modifiability, DNA nanomaterials have become increasingly popular in cell fluorescence imaging in recent years. In addition, DNA nanomaterials can be combined with the cell membrane in a specific manner to enable the real-time imaging of signal molecules on the cell membrane, allowing for the real-time monitoring of disease occurrence and progression. This article examines the recent application of DNA nanomaterials for fluorescence imaging on cell membranes. First, we present the conditions for imaging DNA nanomaterials in the cell membrane microenvironment, such as the ATP, pH, etc. Second, we summarize the imaging applications of cell membrane receptors and other molecules. Finally, some difficulties and challenges associated with DNA nanomaterials in the imaging of cell membranes are presented. [ABSTRACT FROM AUTHOR]

Graphene quantum dots (GQDs) possess potential properties for the targeted transport and tracking of anticancer medication to tumor cells. For this purpose, the synthesized GQDs were decorated with folic acid (FA) and methoxy polyethylene glycol (mPEG2000), and finally loaded with tamoxifen (TMX) drug. The synthesized nano‐drug was characterized using FTIR, XRD, UV‐Vis, PL, HRTEM, FESEM, and DLS analytical devices. Based on the obtained data, the average hydrodynamic diameter of particles dissolved in water was 294.7 nm and the size of dehydrated particles was between 53 and 210 nm. PL data showed that prepared nanoparticles have an emission wavelength of 438 nm, which is in the blue fluorescent wavelength range, thus making these nanoparticles suitable for cell imaging. The encapsulation efficiency and loading percentage of tamoxifen in nanoparticles were calculated at about 52.5 % and 30 %, respectively, and cumulative drug release reached 89 % within 42 hours. The cytotoxicity effects of nanoparticles were investigated. According to IC50 results, the targeted mPEG‐GQDs‐FA/TMX (TMX‐FPGs) nano‐drug was more toxic than free TMX on MCF‐7 cells and had reduced side effects on healthy HDF cells. TMX‐FPGs induced apoptosis cell death, significantly. The confocal imaging experiments showed that TMX‐FPGs are appropriate for monitoring and targeting MCF‐7 cells. [ABSTRACT FROM AUTHOR]

A new coumarin based fluorescent switch PCEH is fabricated which displays high selective sensing towards Al3+ among other metal cations at physiological pH. On gradual addition of Al3+, PCEH shows a brilliant "turn-on" emission enhancement in MeOH/H2O (4/1, v/v) solution. This new fluorescent switch is proven to be a reversible probe by gradual addition of F− into the PCEH-Al3+ solution. Detection limit as well as binding constant values are calculated to be in the order of 10–9 M and 104 M−1 respectively. We have also explored its potential as a biomarker in the application of live cell imaging using breast cancer cells (MDA-MB-231 cell). [ABSTRACT FROM AUTHOR]

This work introduces a novel multifunctional system called UPIPF (upconversion‐polydopamine‐indocyanine‐polyethylene‐folic) for upconversion luminescent (UCL) imaging of cancer cells using near‐infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR‐triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP‐polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)‐modified folic acid (FA) is incorporated into the UCNP‐polydopamine‐indocyanine‐green (UCNP@PDA‐ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA‐ICG‐PEG‐FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real‐time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT‐assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers. [ABSTRACT FROM AUTHOR]

Recently, research incorporating the benefits of deep learning in the application of cancer cell classification and analysis has been actively conducted. In this paper, we investigated examples of binary-class classification and multi-class classification of cancer cell image data of commonly occurring types of cancer worldwide, such as cervical cancer, breast cancer, lung cancer, and colon cancer, using convolutional neural networks (CNNs) models. For instance, some studies explored the utilization of transfer learning, leveraging a pre-trained CNN model is used as a starting point for additional training on a specific cancer cell dataset. Cancer cells have irregular and abnormal growth, making accurate classification challenging. The application of deep learning techniques, such as CNN, for cancer cell classification has been able to solve these complex analysis problems and enable fast cancer cell classification results, leading to early detection of cancer. Indeed, most of the studies in this paper achieved high performance using CNN models, and this approach enables faster and more accurate confirmation of cancer cell classification results, leading to early detection of cancer. This shows the current trend of applying deep learning in the application of cancer cell classification and demonstrates the significant potential of deep learning to contribute to cancer research. Overall, we provide an overview of the current trend of applying deep learning in the field of cancer cell classification and expect that deep learning will open the way for more effective cancer diagnosis and treatment in the future. [ABSTRACT FROM AUTHOR]

In an effort to enhance the antitumor efficacy of breast cancer treatment, the chemotherapeutic agent Paclitaxel (PTX) was encapsulated within hyaluronic acid (HA) modified hollow mesoporous silica (HMSNs). In vitro drug release assays showed that the resulting formulation, Eu-HMSNs-HA-PTX, exhibited enzyme-responsive drug release. In addition, cell cytotoxicity and hemolysis assays demonstrated the favorable biocompatibility of both Eu-HMSNs and Eu-HMSNs-HA. Notably, compared to Eu-HMSNs alone, Eu-HMSNs-HA showed enhanced accumulation within CD44-expressing cancer cells (MDA-MB-231). As anticipated, apoptosis experiments indicated that Eu-HMSNs-HA-PTX displayed significantly greater cytotoxicity toward MDA-MB-231 cells than non-targeted Eu-HMSNs-PTX and free PTX. In conclusion, Eu-HMSNs-HA-PTX demonstrated excellent anticancer effects and holds promise as a potent candidate for the efficient therapy of breast cancer. [Display omitted] • The Eu-HMSNs-HA-PTX as a multifunctional theranostic nanoplatform were successively constructed by surface modification with HA onto Eu-HMSNs and further loading with PTX. • The as-prepared Eu-HMSNs-HA/PTX displayed good biocompatibility and specific targeting capability to CD44-expressing cancer cell (MDA-MB-231). • Cell cytotoxicity and hemolysis assay results indicated the good biocompatibility of Eu-HMSNs and Eu-HMSNs-HA. • In vitro drug release indicated that Eu-HMSNs-HA-PTX performed enzyme-responsive drug release. • The apoptosis experiments indicated that Eu-HMSNs-HA-PTX displayed a significant cytotoxicity of MDA-MB-231 cells and may serve as a promising candidate for the efficient therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Aza-BODIPY biotin-based nano-self-assembly has been designed with a biotin receptor for selective NIR turn-on fluorescence activity against cancer cells. The nanostructured aza-BODIPY assemblies exhibit distinctive fluorescence characteristics via an avidin-induced partial disintegration process. The in vitro studies for nanoprobes NSA-DPR1a and NSA-DPR1b showed effective recognition and can discriminate biotin receptor-positive cancer cells (MDA-MB-231 and MCF7) compared to non-cancerous cells (MCF10A). [ABSTRACT FROM AUTHOR]

Aim: To evaluate the application of an artificial neural network in the detection of malignant cells in effusion samples. Materials and Methods: In this retrospective study, we selected 90 cases of effusion cytology samples over 2 years. There were 52 cases of metastatic adenocarcinoma and 38 benign effusion samples. In each case, an average of five microphotographs from the representative areas were taken at 40× magnification from Papanicolaou‐stained samples. A total of 492 images were obtained from these 90 cases. We applied a deep convolutional neural network (DCNN) model to identify malignant cells in the cytology images of effusion cytology smears. The training was performed for 15 epochs. The model consisted of 783 layers with 188 convolution‐max pool layers in between. Results: In the test set, the DCNN model correctly identified 54 of 56 images of benign samples and 49 out of 56 images of malignant samples. It showed 88% sensitivity, 96% specificity and 96% positive predictive value in the screening of malignant cases in effusion. The area under the receiver operating curve was 0.92. Conclusion: DCNN is a unique technology that can detect malignant cells from cytological images. The model works rapidly and there is no bias in cell selection or feature extraction. The present DCNN model is promising and can have a significant impact on the diagnosis of malignancy in cytology. [ABSTRACT FROM AUTHOR]

The low oxygen dependence of type I photosensitizers (PSs) has made them a popular choice for treating solid tumors. However, the drawbacks of poor water solubility, short emission wavelength, poor stability, and inability to distinguish cancer cells from normal cells limit the application of most type I PSs in clinical therapy. Thereby, developing novel type I PSs for overcoming these problems is an urgent but challenging task. Herein, by utilizing the distinctive structural characteristics of anion‐π+ interactions, a highly water‐soluble type I PS (DPBC‐Br) with aggregation‐induced emission (AIE) characteristic and near‐infrared (NIR) emission is fabricated for the first time. DPBC‐Br displays remarkable water solubility (7.3 mM) and outstanding photobleaching resistance, enabling efficient and precise differentiation between tumor cells and normal cells in a wash‐free and long‐term tracking manner via NIR‐I imaging. Additionally, the superior type I reactive oxygen species (ROS) produced by DPBC‐Br provide both specific killing of cancer cells in vitro and inhibition of tumor growth in vivo, with negligible systemic toxicity. This study rationally constructs a highly water‐soluble type I PS, which has higher reliability and controllability compared with conventional nanoparticle formulating procedures, offering great potential for clinical cancer treatment. [ABSTRACT FROM AUTHOR]

The low oxygen dependence of type I photosensitizers (PSs) has made them a popular choice for treating solid tumors. However, the drawbacks of poor water solubility, short emission wavelength, poor stability, and inability to distinguish cancer cells from normal cells limit the application of most type I PSs in clinical therapy. Thereby, developing novel type I PSs for overcoming these problems is an urgent but challenging task. Herein, by utilizing the distinctive structural characteristics of anion‐π+ interactions, a highly water‐soluble type I PS (DPBC‐Br) with aggregation‐induced emission (AIE) characteristic and near‐infrared (NIR) emission is fabricated for the first time. DPBC‐Br displays remarkable water solubility (7.3 mM) and outstanding photobleaching resistance, enabling efficient and precise differentiation between tumor cells and normal cells in a wash‐free and long‐term tracking manner via NIR‐I imaging. Additionally, the superior type I reactive oxygen species (ROS) produced by DPBC‐Br provide both specific killing of cancer cells in vitro and inhibition of tumor growth in vivo, with negligible systemic toxicity. This study rationally constructs a highly water‐soluble type I PS, which has higher reliability and controllability compared with conventional nanoparticle formulating procedures, offering great potential for clinical cancer treatment. [ABSTRACT FROM AUTHOR]

Due to the immense biological significance of pH in diverse living systems, the design, synthesis, and development of pH chemosensors for pH monitoring has been a very active research field in recent times. In this review, we summarize the designing strategies, sensing mechanisms, biological and environmental applications of fluorogenic and chromogenic pH chemosensors of the last three years (2018–2020). We categorized these pH probes into seven types based on their applications, including 1) Cancer cell discriminating pH probes; 2) Lysosome targetable pH probes; 3) Mitochondria targetable pH probes; 4) Golgi body targetable pH probes; 5) Endoplasmic reticulum targetable pH probes; 6) pH probes used in nonspecific cell imaging; and 7) pH probes without cell imaging. All these different categories exhibit diverse applications of pH probes in biological and environmental fields. [ABSTRACT FROM AUTHOR]

Live-cell imaging with fluorescence microscopy is a powerful tool, especially in cancer research, widely-used for capturing dynamic cellular processes over time. However, light-induced toxicity (phototoxicity) can be incurred from this method, via disruption of intracellular redox balance and an overload of reactive oxygen species (ROS). This can introduce confounding effects in an experiment, especially in the context of evaluating and screening novel therapies. Here, we aimed to unravel whether phototoxicity can impact cellular homeostasis and response to non-thermal plasma (NTP), a therapeutic strategy which specifically targets the intracellular redox balance. We demonstrate that cells incorporated with a fluorescent reporter for live-cell imaging have increased sensitivity to NTP, when exposed to ambient light or fluorescence excitation, likely through altered proliferation rates and baseline intracellular ROS levels. These changes became even more pronounced the longer the cells stayed in culture. Therefore, our results have important implications for research implementing this analysis technique and are particularly important for designing experiments and evaluating redox-based therapies like NTP. [ABSTRACT FROM AUTHOR]

Many cancer cell lines are aneuploid and heterogeneous, with multiple karyotypes co-existing within the same cell line. Karyotype heterogeneity has been shown to manifest phenotypically, thus affecting how cells respond to drugs or to minor differences in culture media. Knowing how to interpret karyotype heterogeneity phenotypically would give insights into cellular phenotypes before they unfold temporally. Here, we re-analyzed single cell RNA (scRNA) and scDNA sequencing data from eight stomach cancer cell lines by placing gene expression programs into a phenotypic context. Using live cell imaging, we quantified differences in the growth rate and contact inhibition between the eight cell lines and used these differences to prioritize the transcriptomic biomarkers of the growth rate and carrying capacity. Using these biomarkers, we found significant differences in the predicted growth rate or carrying capacity between multiple karyotypes detected within the same cell line. We used these predictions to simulate how the clonal composition of a cell line would change depending on density conditions during in-vitro experiments. Once validated, these models can aid in the design of experiments that steer evolution with density-dependent selection. [ABSTRACT FROM AUTHOR]

Mutated cells may constitute a source of cancer. As an effective approach to quantifying the extent of cancer, cell image segmentation is of particular importance for understanding the mechanism of the disease, observing the degree of cancer cell lesions, and improving the efficiency of treatment and the useful effect of drugs. However, traditional image segmentation models are not ideal solutions for cancer cell image segmentation due to the fact that cancer cells are highly dense and vary in shape and size. To tackle this problem, this paper proposes a novel U-Net-based image segmentation model, named U-Net_dc, which expands twice the original U-Net encoder and decoder and, in addition, uses a skip connection operation between them, for better extraction of the image features. In addition, the feature maps of the last few U-Net layers are upsampled to the same size and then concatenated together for producing the final output, which allows the final feature map to retain many deep-level features. Moreover, dense atrous convolution (DAC) and residual multi-kernel pooling (RMP) modules are introduced between the encoder and decoder, which helps the model obtain receptive fields of different sizes, better extract rich feature expression, detect objects of different sizes, and better obtain context information. According to the results obtained from experiments conducted on the Tsinghua University's private dataset of endometrial cancer cells and the publicly available Data Science Bowl 2018 (DSB2018) dataset, the proposed U-Net_dc model outperforms all state-of-the-art models included in the performance comparison study, based on all evaluation metrics used. [ABSTRACT FROM AUTHOR]

The development of site‐specific, target‐selective and biocompatible small molecule ligands as a fluorescent tool for real‐time study of cellular functions of RNA G‐quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm‐specific and RNA G4‐selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA. These G4s are recognized as human cancer hallmarks. Moreover, intracellular competition studies with BRACO19 and PDS, and the colocalization study with G4‐specific antibody (BG4) in HeLa cells may support that the ligand selectively binds to G4s in cellulo. Furthermore, the ligand was demonstrated for the first time in the visualization and monitoring of dynamic resolving process of RNA G4s by the overexpressed RFP‐tagged DHX36 helicase in live HeLa cells. [ABSTRACT FROM AUTHOR]

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N′-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N′-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl− or I−) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 μM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 μM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead. [ABSTRACT FROM AUTHOR]

Purpose: RNA:DNA hybrids are co-transcriptional products with acknowledged cytoplasmic pro-inflammatory role as activators of the cGAS-STING pathway. We recently proved them also as radiation-induced senescence messages for the abscopal effect mediation, demonstrating the need for a functional p53 for their production and release in A549 and H1299 tumour cells. However, little is known about their role under different stress conditions, especially in cancer cells. Methods: In this work, we open the investigation making use of automated quantitative imaging to characterize the hybrid subcellular distribution in HeLa cells grown under different oxygen pressures or exposed to different ionizing radiation doses. After cell imaging by confocal fluorescent microscopy, we apply automated imaging methods developed on purpose to quantify hybrid foci and nuclear cluster intensity, regional and local density and dimension. Results: We show that alteration of culture oxygenation increases hybrid cytoplasmic presence, especially when caused by an hyperoxic environment, with evident hybrid gathering at the cell membrane. Ionizing radiations always fail to increase hybrids, in accordance with the absence of functional p53 in HeLa cells. However, dose-dependent effects are still evident and suggest a threshold dose of 7.5 Gy for remarkable hybrid reduction. Conclusion: Together with our previous results, these data demonstrate for the first time that different types of stress can increase hybrid production in cancer cells and by at least two different pathways, one p53-dependent triggerable by ionizing radiations and one p53-independent triggerable by oxidative stress. Together, our findings provide a starting point for understanding hybrid role in tumour stress response. [ABSTRACT FROM AUTHOR]

A near-infrared fluorescent probe (IC-V) for detecting viscosity is constructed. The probe has a large Stokes shift (170 nm) and an about 180-fold increase in fluorescence intensity at 700 nm. In addition, IC-V can not only distinguish cancer cells from normal cells, but also monitor viscosity in normal mice and tumor-bearing mice. [ABSTRACT FROM AUTHOR]

The development of carbon dots via a green synthesis approach from natural products is one of the most researched areas nowadays. Herein, we present the synthesis of Piper longum leaves-derived aqueous carbon dots (PLACDs) via the simplest ecofriendly hydrothermal carbonization method. The PLACDs exhibited excitation-dependent emission behavior with maximum emission at 450 nm at an excitation wavelength of 365 nm. The High-Resolution Transmission Electron Microscopy results showed a quasi-spherical shape with an average size of 4.121 nm. The sharp diffractions of X-ray diffraction revealed its nanocrystalline property. The Energy Dispersive X-ray spectra reflected the presence of carbon, nitrogen, and oxygen. The Fourier-Transform Infrared Spectroscopy disclosed the existence of –OH, –C=C, –C=O, and –C–O–C groups. The PLACDs presented excellent biocompatibility against B16F10 (melanoma) and SiHa (cervical carcinoma) cells lines with concentration-dependent in vitro bioimaging results. It also exhibited antiradical activity with the IC50 value of 0.499 mg/mL and 0.051 mg/mL against DPPH and ABTS.+, respectively. It showed Fe3+ sensing with a lower limit of detection of 0.673 μM. Further, the PLACDs displayed excellent bacterial biocompatibility, pH-dependent fluorescence property, fluorescent ink property, photostability, physical, chemical, and thermal stability. [ABSTRACT FROM AUTHOR]

Possessing dual-targeted agents toward the lysosome and cancer cells, a ternary supramolecular assembly was constructed by a morpholine-modified permethyl β-cyclodextrin, sulfonated porphyrin, and folic acid-modified chitosan via multivalent interactions. As compared with free porphyrin, the obtained ternary supramolecular assembly showed promoted photodynamic effect and achieved dual-targeted precise imaging in cancer cells. [ABSTRACT FROM AUTHOR]

Probes allowing high‐contrast discrimination of cancer cells and effective retention are powerful tools for the early diagnosis and treatment of cancer. However, conventional small‐molecule probes often show limited performance in both aspects. Herein, we report an ingenious molecular engineering strategy for tuning the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl leads to the increased brightness and reduced cellular uptake of dyes, and this change can be reversed by amino acetylation. Moreover, these modifications allow cancer cells to take up more dyes than normal cells (16‐fold) through active transport. Specifically, we further improve the signal contrast (56‐fold) between cancer and normal cells by constructing activatable probes and confirm that the released fluorophore can remain in cancer cells with extended time, enabling long‐term and specific tumor imaging. [ABSTRACT FROM AUTHOR]

Probes allowing high‐contrast discrimination of cancer cells and effective retention are powerful tools for the early diagnosis and treatment of cancer. However, conventional small‐molecule probes often show limited performance in both aspects. Herein, we report an ingenious molecular engineering strategy for tuning the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl leads to the increased brightness and reduced cellular uptake of dyes, and this change can be reversed by amino acetylation. Moreover, these modifications allow cancer cells to take up more dyes than normal cells (16‐fold) through active transport. Specifically, we further improve the signal contrast (56‐fold) between cancer and normal cells by constructing activatable probes and confirm that the released fluorophore can remain in cancer cells with extended time, enabling long‐term and specific tumor imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] Therapeutic modalities and drug formulations play a crucial and prominent role in actualizing effective treatment and radical cures of tumors. However, the therapeutic efficiency was severely limited by tumor recurrence and complex multi-step preparation of formulation. Therefore, the exploration of novel nanoparticles via a simple and green synthesis process for conquering traditional obstacles and improving therapeutic efficiency is an appealing, yet remarkably challenging task. Herein, a universal nanoplatform allows all cancerous cell-targeting, acid-responsive, cell imaging, synergistic chemotherapy, and nucleolar targeted phototherapy function was tactfully designed and constructed by using chemotherapeutic agents ursolic acid (UA), sorafenib (SF), and carbon dots (CDs) photosensitizers (PSs). The designed US NPs were formed by self-assembly of UA and SF associated with electrostatic, π-π stacking, and hydrophobic interactions. After hydrogen bonding reaction with CDs, the obtained (denoted as USC NPs) have a relatively uniform size of an average 125.6 nm, which facilitated the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free CDs solution. Both in vitro and in vivo studies revealed that the advanced platform commenced synergistic anticancer therapeutic potency, imperceptible systematical toxicity, and remarkable reticence towards drug-resistant cancer cells. Moreover, the CDs PSs possess intrinsic nucleolus-targeting ability. Taken together, this theranostics system can fully play the role of "killing three birds with one stone" in a safe manner, implying a promising direction for exploring treatment strategies for cancer and endowing them with great potential for future translational research and providing a new vision for the advancing of an exceptionally forceful protocol for practical cancer therapy. [ABSTRACT FROM AUTHOR]

Flavonoid-containing Gratiola officinalis extract has been studied in relation to breast carcinoma and human cervical cancer cells in encapsulated and native form. Encapsulation was realized in polymer shells, which were formed by the layer-by-layer method using sequential adsorption of poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) on the destructible cores. The extract was prepared by the author's method and characterized using high performance liquid chromatography. By means of optical and fluorescent microscopy, cell changes under the action of pure and encapsulated extracts were comprehensively studied, and statistical analysis was carried out. Cells were stained with propidium iodide, acridine orange, and Hoechst 33258. A fluorescence microscope with a digital video camera were used for cell imaging. The encapsulated extract caused 100% death of breast cancer SKBR-3 cells and 34% death of cervical cancer HeLa cells and prevented the formation of autophagosomes in both cultures. Analysis of the viability and morphological features of tumor cells under the action of microencapsulated extract allows us to consider microencapsulation as an effective strategy for delivering Gratiola officinalis extract to tumor cells and a promising way to overcome the protective autophagy. [ABSTRACT FROM AUTHOR]

Chemotaxis, regulated by oscillatory signals, drives critical processes in cancer metastasis. Crucial chemoattractant molecules in breast cancer, CXCL12 and EGF, drive the activation of ERK and Akt. Regulated by feedback and crosstalk mechanisms, oscillatory signals in ERK and Akt control resultant changes in cell morphology and chemotaxis. While commonly studied at the population scale, metastasis arises from small numbers of cells that successfully disseminate, underscoring the need to analyze processes that cancer cells use to connect oscillatory signaling to chemotaxis at single-cell resolution. Furthermore, little is known about how to successfully target fast-migrating cells to block metastasis. We investigated to what extent oscillatory networks in single cells associate with heterogeneous chemotactic responses and how targeted inhibitors block signaling processes in chemotaxis. We integrated live, single-cell imaging with time-dependent data processing to discover oscillatory signal processes defining heterogeneous chemotactic responses. We identified that short ERK and Akt waves, regulated by MEK-ERK and p38-MAPK signaling pathways, determine the heterogeneous random migration of cancer cells. By comparison, long ERK waves and the morphological changes regulated by MEK-ERK signaling, determine heterogeneous directed motion. This study indicates that treatments against chemotaxis in consider must interrupt oscillatory signaling. [ABSTRACT FROM AUTHOR]

Cell migration is a pivotal biological process, whose dysregulation is found in many diseases including inflammation and cancer. Advances in microscopy technologies allow now to study cell migration in vitro, within engineered microenvironments that resemble in vivo conditions. However, to capture an entire 3D migration chamber for extended periods of time and with high temporal resolution, images are generally acquired with low resolution, which poses a challenge for data analysis. Indeed, cell detection and tracking are hampered due to the large pixel size (i.e., cell diameter down to 2 pixels), the possible low signal-to-noise ratio, and distortions in the cell shape due to changes in the z-axis position. Although fluorescent staining can be used to facilitate cell detection, it may alter cell behavior and it may suffer from fluorescence loss over time (photobleaching). Here we describe a protocol that employs an established deep learning method (U-NET), to specifically convert transmitted light (TL) signal from unlabeled cells imaged with low resolution to a fluorescent-like signal (class 1 probability). We demonstrate its application to study cancer cell migration, obtaining a significant improvement in tracking accuracy, while not suffering from photobleaching. This is reflected in the possibility of tracking cells for three-fold longer periods of time. To facilitate the application of the protocol we provide WID-U, an open-source plugin for FIJI and Imaris imaging software, the training dataset used in this paper, and the code to train the network for custom experimental settings. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to identify the benefits in image contrast enhancement of Folic acid-Cysteamine conjugated gold nanoparticles (FA-Cys-AuNPs) by comparing Contrast to Noise ratio (CNR) of gold nanoparticles (AuNPs) to iodinated compound CT images. The CNR was assessed in different tube voltages, concentrations, and incubation times in nasopharyngeal KB cancer cells. Material and Methods: FA-Cys-AuNPs and Omnipaque suspension were scanned at different concentration ranges (500-2000 µg/ml) and energy ranges (80-140 kVp) with CT imaging modality. FA-Cys-AuNPs and AuNPs were incubated in nasopharyngeal cancer cells at different incubation times (6, 12, and 24 h) and concentration ranges (200-500 µM). Finally, the contrast enhancement was assessed using CNR value at different tube voltages. Results: Results showed that the formed FA-Cys-AuNPs with an Au core size of 15 nm in all concentrations and tube potentials from 80 to 140 kVp display greater CNR than Omnipaque. The CNR value was increased by increasing concentration and energy. At 140 kVp and 2000 µg/ml, the CNR value of FA-Cys-AuNPs was 2.25 times greater than Omnipaque. At 140 kVp, 500 µM and 24 h incubation, the CNR values of targeted cells were approximately 1.5 times higher than non-targeted cells. At 140 kVp, and 500 µM, the CNR value of targeted cells with 24 h incubation time was 2.66 times greater than the targeted cells incubated with 6 h. Conclusion: These findings suggested that the designed FA-Cys-AuNPs could be a good candidate contrast agent for molecular CT imaging. [ABSTRACT FROM AUTHOR]

DNA micelles formed by hydrophobic, self-assembly of amphiphilic DNA monomers have enormous potential in biological imaging owing to its unique and programmable, three-dimensional nanostructure. Herein, we rationally design double-stranded DNA oligonucleotides with two cholesterols that can spontaneously form the lipid-mediated DNA micelles and generate the high fluorescence signal after the formation of DNA-templated copper nanoclusters (CuNCs). Furthermore, the DNA aptamer specific to MUC1 protein, aberrantly overexpressed on the surface of cancer cells, is attached to lipid-mediated DNA micelles to confer the selectivity towards the target cancer cells. With the well-defined DNA nanostructures, the cell membrane of MUC1-positive cancer cells are stained by CuNCs exhibiting an intense, red fluorescence signal, which are clearly distinguished from MUC1-negative cancer cells. This approach may not only expand the application scope of both DNA micells and CuNCs, especially in the area of cellular imaging, but also provides a basis for developing other types of DNA nanostructures to detect target biomarkers. [ABSTRACT FROM AUTHOR]

The current work demonstrated an in vitro model of diastase capped gold nanoparticles (Au NPs) and nanoplates (Au NPts) as unique contrast agents for molecular imaging and photothermal cancer therapy, respectively. The Au NPs/Au NPts were fabricated and conjugated with monoclonal antibodies of anti-epidermal growth factor receptor (anti-EGFR). Anti-EGFR-AuNPs bioconjugate was studied for molecular imaging allowing to interact with the nasopharyngeal carcinoma (CNE2 cells). Confocal immunofluorescence microscopic results revealed the increased scattering and reflectance properties of CNE2 cells after attachment and localization of Anti-EGFR-AuNPs bioconjugate on the cell surface, consequently providing the good optical contrast for the cancer cell imaging. On the other hand, Anti-EGFR-Au NPts were studied for photothermal applications using two malignant oral epithelial cell lines (HSC 3 and HOC 313 clone 8) and a nonmalignant epithelial cell line (HaCat), which revealed that the malignant cells require almost half of the laser energy to be photothermally eliminated after exposure to continuous red laser at 800 nm when compared with the nonmalignant cells. Further, the present approach may have potential for development of NPs for selective photothermal therapy and a successful diagnostics of cancer cell for bioimaging applications. [ABSTRACT FROM AUTHOR]

ZnO nanoparticles have various characteristics that make them attractive to be used in many medical applications like a cancer diagnosis. It can be used as a nanoprobe for targeting different types of cancer cells in vitro as a cancer cell recognition system. The present study aims to investigate the permeability of ZnO NPs through both normal and cancerous cell lines in humans. In vitro experiments for ZnO NPs inside the environment of living cells have been described, which would contribute to the visualization of nanoparticles as cancer diagnostic and scanning techniques. MCF7, AMJ13, and RD cancer cells, and also the normal breast cell line HBL, were used in in vitro imaging experiments. The findings revealed that ZnO NPs specifically incorporated within tumor cells while accumulating less inside normal cells. Our findings show that ZnO NPs may be identified inside cancer cells after 1 h of exposure and can endure up to 3 h, providing them appropriate for tumor cell imaging. The findings showed that ZnO NPs might be employed as an alternate fluorophore for diagnostic imaging in the early identification of solid cancers. Therefore, here we studied in vitro applications of ZnO NPs and their beneficial use as a diagnostic tool for cancer cell lines rather than normal cells. Taken together, ZnO NPs can be used as good targeting NPs for the development of imaging agents for early diagnosis of cancers. [ABSTRACT FROM AUTHOR]

Lack of appropriate tools for visualizing cell membrane molecules at the nanoscale in a non‐invasive and label‐free fashion limits our understanding of many vital cellular processes. Here, we use tip‐enhanced Raman spectroscopy (TERS) to visualize the molecular distribution in pancreatic cancer cell (BxPC‐3) membranes in ambient conditions without labelling, with a spatial resolution down to ca. 2.5 nm. TERS imaging reveals segregation of phenylalanine‐, histidine‐, phosphatidylcholine‐, protein‐, and cholesterol‐rich BxPC‐3 cell membrane domains at the nm length‐scale. TERS imaging also showed a cell membrane region where cholesterol is mixed with protein. Interestingly, the higher resolution TERS imaging revealed that the molecular domains observed on the BxPC‐3 cell membrane are not chemically "pure" but also contain other biomolecules. These results demonstrate the potential of TERS for non‐destructive and label‐free imaging of cell membranes with nanoscale resolution. [ABSTRACT FROM AUTHOR]

Lack of appropriate tools for visualizing cell membrane molecules at the nanoscale in a non‐invasive and label‐free fashion limits our understanding of many vital cellular processes. Here, we use tip‐enhanced Raman spectroscopy (TERS) to visualize the molecular distribution in pancreatic cancer cell (BxPC‐3) membranes in ambient conditions without labelling, with a spatial resolution down to ca. 2.5 nm. TERS imaging reveals segregation of phenylalanine‐, histidine‐, phosphatidylcholine‐, protein‐, and cholesterol‐rich BxPC‐3 cell membrane domains at the nm length‐scale. TERS imaging also showed a cell membrane region where cholesterol is mixed with protein. Interestingly, the higher resolution TERS imaging revealed that the molecular domains observed on the BxPC‐3 cell membrane are not chemically "pure" but also contain other biomolecules. These results demonstrate the potential of TERS for non‐destructive and label‐free imaging of cell membranes with nanoscale resolution. [ABSTRACT FROM AUTHOR]

The inhibition of healthy cells creating improper controlling process of the human body system indicates the occurrence of growth of cancerous cells. The cluster of such cells leads to the development of tumor. The observation of this type of abnormal skin pigmentation is done using an effective tool called Dermoscopy. However, these dermatoscopic images possess a great challenge for diagnosis. Considering the characteristics of dermatoscopic images, transfer learning is an appropriate approach of automatically classifying the images based on the respective categories. An automatic identification of skin cancer not only saves human life but also helps in detecting its growth at an earlier stage which saves medical practitioner's effort and time. A newly predicted model has been proposed for classifying the skin cancer as benign or malignant by DCNN with transfer learning and its pre-trained models such as VGG 16, VGG 19, ResNet 50, ResNet 101, and Inception V3. The proposed methodology aims at examining the efficiency of pre-trained models and transfer learning approach for the classification tasks and opens new dimensions of research in the field of medicines using imaging technique which can be implementable in real-time applications. [ABSTRACT FROM AUTHOR]

Theranostics play an important role in cancer treatment due to its realized real-time tracking of therapeutic efficacy in situ. In this work, we have designed and synthesized a terpyridine-modified pillar [5]arenes (TP5). By the coordination of terpyridine and Zn2+, the complex TP5/Zn was obtained. Then, supramolecular amphiphile can be constructed by using host–guest complexation between a polyethylene glycol contained guest (PM) and TP5/Zn. Combining the fluorescence properties from the terpyridine group and the amphiphilicity from the system, the obtained TP5/Zn/PM can further be self-assembled into fluorescent particles with diameters of about 150 nm in water. The obtained particles can effectively load anti-cancer drugs and realize living cell imaging and a precise release of the drugs. [ABSTRACT FROM AUTHOR]

Aptamers are a class of single‐stranded DNA or RNA oligonucleotides that can exclusively bind to various targets with high affinity and selectivity. Regarded as "chemical antibodies", aptamers possess several intrinsic advantages, including easy synthesis, convenient modification, high programmability, and good biocompatibility. In recent decades, many studies have demonstrated the superiority of aptamers as molecular tools for various biological applications, particularly in the area of cancer theranostics. In this review, we focus on recent progress in developing aptamer‐based strategies for the precise analysis and treatment of cancer cells. [ABSTRACT FROM AUTHOR]

Environment‐responsive in situ synthesis of molecular fluorescent dyes is challenging. Herein, we develop a photoextension strategy to make trimethine cyanines with decent conversion efficiency (up to 81 %) using 1‐butyl 2,3,3‐trimethyl 3H‐indole derivatives as the sole precursors, and demonstrate a free radical mechanism. In the inducer‐extension stage, free radicals and reactive oxygen species (ROS) were able to mediate similar reactions with no assistance of light. We explored a Mito‐extension strategy to in situ synthesize trimethine cyanines in the living cells. The cellular ROS‐dependence provided a foundation for preferential cyanine expression in cancer cells. Finally, we applied an iodized precursor as an intrinsic ROS‐activated theranostic agent that integrated mitochondria‐targeted cyanine synthesis, cell imaging and phototherapy. [ABSTRACT FROM AUTHOR]

Environment‐responsive in situ synthesis of molecular fluorescent dyes is challenging. Herein, we develop a photoextension strategy to make trimethine cyanines with decent conversion efficiency (up to 81 %) using 1‐butyl 2,3,3‐trimethyl 3H‐indole derivatives as the sole precursors, and demonstrate a free radical mechanism. In the inducer‐extension stage, free radicals and reactive oxygen species (ROS) were able to mediate similar reactions with no assistance of light. We explored a Mito‐extension strategy to in situ synthesize trimethine cyanines in the living cells. The cellular ROS‐dependence provided a foundation for preferential cyanine expression in cancer cells. Finally, we applied an iodized precursor as an intrinsic ROS‐activated theranostic agent that integrated mitochondria‐targeted cyanine synthesis, cell imaging and phototherapy. [ABSTRACT FROM AUTHOR]

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging. [ABSTRACT FROM AUTHOR]

A purely organic supramolecular assembly emitting three‐photon room‐temperature phosphorescence (RTP) is constructed from a macrocyclic host, cucurbit[8]uril (CB[8]), and 4‐bromophenyl pyridine salt having an alkyl chain length of 6 or 12 carbon atoms (6C and 12C, respectively). Benefiting from macrocyclic host confined guests, the encapsulation of 12C and 6C in the CB[8] cavity results in three‐photon absorption and subsequent near‐infrared (NIR) phosphorescence emission. Notably, secondary assembly with sulfonated β‐cyclodextrin (SCD) further enhances the phosphorescence emission of the multilevel supramolecular assembly. NIR‐delayed fluorescence via a light‐harvesting phosphorescent energy transfer system is achieved by adding Nile blue as a substrate. Comparison of 12C/CB[8]/SCD and 6C/CB[8]/SCD shows that a long hydrophobic layer is more conducive to stabilizing NIR‐delayed fluorescence emission. These findings indicate that multilevel supramolecular assemblies can be used for three‐photon‐excited NIR‐delayed fluorescence and RTP imaging of cancer cells, which greatly expands the biological applications of pure organic RTP materials. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) have emerged as a hot target for cancer therapeutics in recent years owing to findings that have shown them to be key organelles involved in maintaining cellular stability and regulating inter-organelle communication through molecular trafficking. LDs emerge from the endoplasmic reticulum (ER) as a form of cellular homeostasis control. We herein report the study of a library of asymmetric squaraines as superior fluorescence probes to track and image LDs in their native state and environment within cancer cells. The probes are highly selective towards LDs and displayed prominent bright fluorescence with just 1 μM probe concentration. They also possess bimodal LD and ER staining capability via the simple diffusion of small lipophilic molecules. The probes almost instantly stained LDs, while the ER staining rate is dependent on the probe's lipophilicity and the incubation duration. These "on-demand" organelle-selective probes are highly desirable tools for revealing the role of LDs in governing many cellular processes, especially in malignant cells. [ABSTRACT FROM AUTHOR]

Cervical cancer is the most prevalent cancer in females. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. However, the underlying molecular mechanism is not known. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). The anti-cancer effect of melatonin was evaluated by MTT assay, cell imaging, colony formation, DAPI, AO/PI, LDH, Flow cytometry, scratch assay, western blot analysis and real-time PCR. Results of DAPI, AO/PI, LDH, and Annexin/PI staining revealed that melatonin induces apoptosis. The results of cell cycle analysis revealed that melatonin arrests the HeLa and SiHa cells in sub-G1 and G1 phases, respectively. Western blot analysis revealed that melatonin downregulated the expression of pro-inflammatory transcription factor, NF-κB and the expression of COX-2 protein, a key mediator in cell proliferation. In addition, melatonin downregulated the expression of an invasive marker, MMP-9, an antiapoptotic protein, Bcl-2, and upregulated the expression of pro-apoptotic protein, Bax at both transcriptional and translational levels. Overall, the results suggest that melatonin exhibited strong anti-cancer therapeutic potential against human cervical cancer cell line progression possibly through inhibition of NF-κB signalling pathway. [ABSTRACT FROM AUTHOR]

Laser emission imaging is an emerging technology, which offers immense potential for revealing biological behavior with enhanced light‐matter interactions and signal contrast. State‐of‐the‐art lasers mostly provide physical information of cells, without being able to perform various biochemical functions or biological information of cell. Here this need is addressed by introducing hybrid liquid crystal microlaser resonators, an approach for label‐free laser emission imaging of secreted molecules associated with various types of cell–environment interaction. Liquid crystal microdroplets are designed as signal amplifiers to report subtle molecular events sandwiched in a Fabry–Pérot microcavity. Through the integration with a galvometer scanner, dynamic information of cell physiological processes is recorded through different lasing wavelengths. The capability of detecting small molecule, redox oxygen species, to larger molecules such as overexpressed proteins is demonstrated by using pancreatic cancer cell line. The capability of monitoring cell responses to anticancer drug is also illustrated. The proposed concept can be extended to multiplexed biolasers for investigating cell signaling, cell–cell interactions, and drug screening. [ABSTRACT FROM AUTHOR]

• We propose deep learning models for classification of cancer cells belonging to different organs on holographic images. • We present self-supervised pretraining and hyperparameter tuning for efficient training on biomedical holographic datasets. • Perform extensive experiments with self-supervised frameworks and compared self-supervised learning with supervised learning and proved the effectiveness of the former for holographic images classification. • Proposed work can be an effective tool for the automatic classification of cancer cells for medical diagnosis using self-supervised learning. Image-based stain-free elliptical cancer cell classification is challenging, due to the inter-class morphological similarity. In this paper, we address the classification of different types of cancer cell lines (lung, breast, bladder, and skin) by utilizing self-supervised learning, and compare it with supervised learning based on convolutional neural network. Digital holography in a microscopic configuration was used to obtain stain-free quantitative phase images representing the intracellular content and morphology of cells. The performance of self-supervised learning in natural images shows promising results, and consistently closes the gap between self-supervised and supervised learning. The ability of self-supervised learning to effectively utilize unlabeled data for training is instrumental in the biomedical domain, where labeled data is scarce. Our goal is to study different self-supervised frameworks of biomedical holographic data, and determine how they can be utilized to advance liquid biopsy for the detection of cancer cells. After extensive experimentation, we conclude that self-supervised learning improves the classification performance on cancer cell datasets, and outperforms supervised learning when training data is limited, which is mostly the case in biomedical imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • The probe P-1 can selectively detect H 2 O 2 with colorimetric change. • the P-1 can be used for on-site and visual detection of H 2 O 2. • The P-1 can image H 2 O 2 in cells and distinguish cancer cells and normal cells. • The P-1 probe was applied to monitor H 2 O 2 of tumor in mice. We designed and developed the probe P-1 for detecting H 2 O 2. The probe can selectively detect H 2 O 2 with colorimetric change. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site and visual detection of H 2 O 2 with satisfactory sensitivity and reliability. The P-1 can image exogenous and endogenous H 2 O 2 in cells and distinguish cancer cells and normal cells by fluorescence image of H 2 O 2 and flow cytometry. Meanwhile, the P-1 probe has been successfully applied to monitor H 2 O 2 levels of tumor in mice, and the results showed the level of H 2 O 2 in tumor tissue increased significantly. Therefore, P-1 provided a potential chemical tool to understand pathological and physiological mechanisms of diseases by imaging H 2 O 2. [ABSTRACT FROM AUTHOR]

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l -Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications. Tris-assisted one-step fabrication of functional F-CDs for specific folate receptor positive-expressed cancer cell imaging. [Display omitted] • F-CDs were fabricated via rich hydroxyl groups Tris to mediate hydrothermal process of FA and L-Arg. • Rich hydroxyl groups of Tris play a vital role in the optical properties and intrinsic targeting ability for FR positive-expressed cancer cell for labeling and tracking. • This study provides an efficient strategy to design fluorescent CDs for extensive applications. [ABSTRACT FROM AUTHOR]