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• 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]

Detecting and neutralizing Pd2+ ions are a significant challenge due to their cytotoxicity, even at low concentrations. To address this issue, various chemosensors have been designed for advanced detection systems, offering simplicity and the potential to differentiate signals from different analytes. Nonetheless, these chemosensors often suffer from limited emission response and complex synthesis procedures. As a result, the tracking and quantification of residual palladium in biological systems and environments remain challenging tasks, with only a few chemosensing probes available for commercial use. In this paper, a straightforward approach for the selective detection of Pd2+ ions is proposed, which involves the design, synthesis, and utilization of a propargylated naphthalene-derived probe (E)-N'-((2-(prop-2-yn-1-yloxy)naphthalen-1-yl)methylene)benzohydrazide (NHP). The NHP probe exhibits sensitive dual-channel colorimetry and fluorescence Pd2+ detection over other tested metal ions. The detection process is performed through a catalytic depropargylation reaction, followed by an excited state intramolecular proton transfer (ESIPT) process, the detection limit is as low as 11.58 × 10−7 M under mild conditions. Interestingly, the resultant chemodosimeter adduct (E)-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide (NHH) was employed for the consecutive detection of CN− ions, exhibiting an impressive detection limit of 31.79 × 10−8 M. Validation of both detection processes was achieved through 1H nuclear magnetic resonance and density functional theory calculations. For real-time applications of the NHP and NHH probes, smartphone-assisted detection, and intracellular detection of Pd2+ and CN− ions within HeLa cells were studied. This research presents a novel naphthalene derivative for visually detecting environmentally toxic Pd2+ and CN− ions. The synthesized probe selectively binds to Pd2+, forming a chemodosimeter. It successfully detects CN− ions through colorimetry and fluorimetry, offering a low detection limit and quick response. Notably, it's the first naphthalene-based small molecule to serve as a dual probe for toxic analytes - palladium and cyanide. Moreover, it effectively detects Pd2+ and CN− intracellularly in cancer cells. [Display omitted] • Probe NHP selectively detects Pd2+ and forms chemodosimeter adduct NHH , showing a specific turn-on response to CN- ions. • The "off-on-off" ESIPT process led to the dual-channel detection of Pd2+ and CN− in an ethanol-H 2 O solution. • Consecutive detection, first of Pd2+ and then of CN-, showed naked-eye visibility, rapid response, and a low detection limit. • The study explored both on-site smartphone-based detection and intracellular detection of Pd2+ and CN- within HeLa cells. [ABSTRACT FROM AUTHOR]

Fluorescent sensors have been widely applied for biosensing, but probes for both multiple analytes sensing and photodynamic therapy (PDT) effect are less reported. In this article, we reported three AIE-based probes anchored with different mass-weight polyethylene glycol (PEG) tails, i.e., TPE-PEG160 , TPE-PEG350 , and TPE-PEG750 , for both adenosine-5′-triphosphate (ATP) and hydrogen sulfide (H 2 S) detection and also cancer cells photodynamic therapy. TPE-PEGn s (n = 160, 350 and 750) contain the tetraphenylethylene-based fluorophore core, the pyridinium and amide anion binding sites, the H 2 S cleavable disulfide bond, and the hydrophilic PEG chain. They exhibit a good amphiphilic property and can self-assemble nona-aggregation with a moderated red emission in an aqueous solution. Importantly, the size of aggregation, photophysical property, sensing ability and photosensitivity of these amphiphilic probes can be controlled by tuning the PEG chain length. Moreover, the selected probe TPE-PEG160 has been successfully used to detect environmental H 2 S and image ATP levels in living cells, and TPE-PEG750 has been used for photodynamic therapy of tumor cells under light irradiation. Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) for both ATP and H 2 S detection and also cancer cells photodynamic therapy have been reported. [Display omitted] • Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) were prepared. • TPE-PEGn s can detect ATP and H 2 S with a high sensitivity and selectivity. • Properties (size, optics, sensing) of TPE-PEGn s can be affected by PEG chain. • TPE-PEG160 can detect environmental H 2 S and image ATP in living cells. • TPE-PEG750 has been used for image-guided killing of cancer cells. [ABSTRACT FROM AUTHOR]

Precise imaging identification of tumor tissues from normal tissues is still challenging. In this study, a new dual-locked near-infrared fluorescent probe BBQ650-SS-BTZHC-E was developed for the discrimination between cancer cells and normal cells. The probe consists of a hemicyanine fluorophore conjugated to an esterase substrate and a quencher connected via a disulfide bond. The esterase substrate blocks the excited state intramolecular proton transfer (ESIPT) process, while the quenching agent forms a Förster resonance energy transfer (FRET) pair with the fluorophore. The fluorescence activation is dependent on the presence of both esterase and glutathione (GSH), resulting in the "ESIPT on" and "FRET off" states, which represent an "AND" logic. The characterizations showed that the kinetics of fluorescence activation are dependent on the concentrations of the two activators with a high specificity. Fluorescent imaging experiments using BBQ650-SS-BTZHC-E successfully distinguished cancer cells (HeLa, 4T1, RAW264.7) from normal cells (HFL1) with high contrast and specificity, and imaged 4T1 tumor on live mice. This study provides a simple platform for the development of dual-locked fluorescent probes for bio-imaging applications. [Display omitted] • A new hemicyanine-derived NIR "AND" logical dual-locked fluorescent probe. • The activation of the fluorescence is based on ESIPT and FRET processes. • The probe distinguished cancer cells from normal cells with high imaging contrast and specificity. • This work represents a platform for dual-locked NIR probes that is easy to synthesize and modify. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB – possess a surface potential of −8 mV and a size of 150 nm – demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance. [ABSTRACT FROM AUTHOR]

A novel NIR probe based on oxazolonaphthoimidazo[1,2- a ]pyridine-malononitrile (ONIM) conjugate linked by vinyl linkage was designed and synthesized for the detection of cyanide ion. [Display omitted] • An orange emitting sensor ONIM (712 nm) with D-π-A framework is synthesized. • The ONIM emission is retained in the solid state. • ONIM could sense cyanide ion without interference of other anions. • Sensing mechanism of cyanide sensing was confirmed by 1H NMR and DFT calculations. • Live cell imaging in human breast cancer cell MDA-MB 231 and as solid state sensor was achieved. Cyanide is undoubtedly dangerous and fast acting chemical employed in various industrial applications with toxic side effects, which raises urgent need for its monitoring. In this context, oxazolonaphthoimidazo[1,2- a ]pyridine-malononitrile (ONIM) conjugate linked by vinyl linkage was designed, synthesized and characterised by FT-IR, NMR and mass spectrometry. The developed probe has been evaluated for the colorimetric and fluorometric detection of cyanide ion. An obvious color change with unique rapid " turn-off " fluorometric response was observed within 5 s upon addition of CN– thus reflecting its better acuteness and sensitivity over other competing anions. The developed probe exhibits a detection limit of 9.54 nM which is very low in comparison to maximum permitable amount of cyanide in drinking water (1.9 µM). The probe is stable within the p H range of 2–9 and suitable for the recognition of CN– in the p H range of 7 to 10, specially at neutral p H conditions. The chemodosimetric approach based detection mechanism was authenticated by 1H NMR titration and DFT calculations. The solid state applications were established by utilising ONIM impregnated TLC plates and filter paper in cyanide recognition. The solid state emissive behaviour of ONIM offers on-spot detection of the cyanide anion. Additionally, the practicability of ONIM has been extended in live cell imaging of CN– in human breast cancer cell (MDA-MB-231), which revealed a " turn-off " fluorescence response for the probe in the presence of CN– ion. [ABSTRACT FROM AUTHOR]

[Display omitted] • A single step of synthesis and assemble of lecithin-derived self-assemble carbon dots. • Enhanced photothermal and photoluminescence property. • Superior Theranostic efficiency after 24 h of incubation with enhanced retention. Photothermal therapy is a promising strategy for killing cancer cells, yet the use of carbon dots as a photothermal agent has limited its use due to the high excretion rate from the cancer cell due to its smaller size of less than 10 nm. In this study, we have developed a strategy for synthesizing self-assembled carbon dots with higher photothermal and lesser excretion from cells. Single-step synthesis of self-assembled carbon dots using thermal degradation method process using lecithin as carbon source. The self-assembly of lecithin-derived carbon dots is induced in the presence of water molecules. Excitingly, lecithin-derived self-assembly of carbon dots (LDSCD) shows superior photothermal efficacy even at low concentrations and fluorescence is red-shifted. Moreover, the LDSCD exhibits higher phototoxicity on incubation with cancer cells for two hours followed by near-infrared light exposure after twenty-four hours. The confocal images of the cells incubated with lecithin-derived self-assembly of carbon dots at two-time intervals (4 and 24 hrs) demonstrated higher retention of self-assembled quantum dots compared to the smaller-size carbon dots (<50 nm). [ABSTRACT FROM AUTHOR]

[Display omitted] • Self-targeted fluorescent carbon dots (CDs) have the potential for cancer cell imaging and therapy. • A new type of CD was synthesized via a hydrothermal method by using pemetrexed carbon precursor as an agonist of folate receptors. • Pemetrexed residues on CDs surface target folate receptors, allowing specific recognition and targeting of breast cancer cells. • CDs show dose-dependent cytotoxicity, potentially affecting tumor cell function and potentially causing cancer cell death in high concentrations. • This work highlights the potential diagnostic, targeting, and therapeutic functions of Self-targeted CDs. Carbon dots (CDs) possess a broad spectrum of applications in chemical, physical, and biomedical research. We are particularly intrigued by the utilization of CDs as fluorescence nanoparticles for the purpose of targeted imaging of tumor cells. Here, we have achieved the one-step synthesis of luminous CDs utilizing pemetrexed (PMX) as the carbon precursor in aqueous environment via the hydrothermal technique. The average size of CDs was about 3.4 nm. The CDs were internalized within 4T1and MCF-7 cell lines. The CDs wasn't exhibited toxicity in 4T1 cell line. However, an increase of co-localization of CDs, and the cytotoxic effects in high concentrations was observed in MCF-7 cells, which probably can result from the interaction of these nanoparticles with the folate receptor (FR). The presence of PMX residuals, analog with FA in CDs resulted in a remarkable ability to specifically target cancer cells and effectively enhance the cellular uptake mediated by FR. This achievement demonstrates significant potential for application in biological and bioimaging research endeavors. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) exerts its therapeutic effects by inducing apoptosis, necrosis, and microvascular damage in tumor cells, but it also causes inflammation and induces the expression of angiogenic factors, accelerating tumor metastasis and proliferation. In this study, aggregation-induced emission (AIE) photosensitizer (PS) for PDT was combined with the cyclooxygenase-2 (COX-2) inhibitor indomethacin (IMC) for cancer-selective imaging and more efficiency in inducing apoptosis in cancer cells. In detail, inhibition of COX-2-mediated AIE PS effectively targeted the Golgi apparatus (GA) of cancer cells to generate large amounts of reactive oxygen species (ROS) in situ, thereby exerting a PDT effect. Specifically, COX-2 and other key enzymes that trigger inflammation and metastasis were significantly inhibited. It had more potent anti-tumor activity (tumor inhibition rate of 64.32 %), as well as anti-metastatic and anti-proliferative effects compared to the use of usual AIE PS. [Display omitted] • TTPI was obtained by combining AIE-PS with the COX-2 inhibitor indomethacin. • TTPI precisely targeted COX-2 in the Golgi with high co-location coefficient. • PDT while inhibiting enzymes that trigger inflammation and metastasis such as COX-2. • The inhibition rate of TTPI in vivo was significantly increased to 64.32 %. [ABSTRACT FROM AUTHOR]

A novel cancer cell and lysosome dual-targeted photosensitizer (PS) termed by BMP was developed for fluorescence imaging and photodynamic therapy (PDT). BMP consists of a porphyrin(Zn) core with appropriate singlet-triplet state distribution enables it to function as an imaging agent as well as a PS, a biotin moiety that can target cancer cells, and a morpholine group specific to lysosomes. Intracellular experiments demonstrated that the dual-targeted photosensitizer BMP could preferably accumulate in cancer cells and subsequently locate within lysosome organelles. Upon irradiation, BMP could generate red fluorescence emission (Φ em = 6.3%) and singlet oxygen (1O 2 , Φ Δ = 55%) for the dual functionality of cell imaging and PDT, respectively. Notably, BMP exhibited much higher photocytotoxicity toward cancer cells (A549 cells) compared to normal cells (BEAS-2B cells). Importantly, 1O 2 produced by BMP induced oxidative damage of lysosomes, and subsequently triggered cell death of A549 cells, as evidenced by the loss of morphological integrity and cell rupture. A cancer cell and lysosome dual-targeted photosensitizer BMP was designed to generate red emission and singlet oxygen (1O 2) simultaneously, which were utilized successfully for dual-targeted fluorescence imaging and photodynamic therapy. [Display omitted] • A dual-targeted photosensitizer was designed and synthesized by modularization. • Biotin acted as a targeting ligand for cancer cells, and morpholine was selected as the lysosome-specific group. • Red fluorescence and singlet oxygen generation were achieved for fluorescence imaging and PDT of cancer cells simultaneously. [ABSTRACT FROM AUTHOR]

As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis. [Display omitted] • A probe (IX-V) has a NIR fluorescence and photoacoustic response to viscosity. • IX-V shows high sensitivity and selectivity for viscosity over other analytes. • This probe can be used in visualizing viscosity change in various living cells. • IX-V can distinguish cancer cells from normal cells co-cultured in one dish. • IX-V is applied for monitoring the viscosity level in mice by dual-modal imaging. [ABSTRACT FROM AUTHOR]