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• A generalized method for effective early diagnosis of pancreatic cancer based on multiple instance learning. • A spatial transformation based on anatomical structures is proposed to reduce the background interference and enhance the detection stability for the learned features. • Instance-level contrastive learning is developed to aggregate different types of tumor features, maintain the tumor feature integrity, and enhance the diagnosis stability. • The method achieves remarkable generalization performance in unseen datasets and is sensitive to tumors smaller than 2 cm in diameter. Pancreatic cancer is a highly malignant cancer type with a high mortality rate. As no obvious symptoms are associated with this cancer type, most of the diagnoses are made when the patients are already in a late stage. In this work, we propose an automated method for effective early diagnosis of pancreatic cancer based on multiple instance learning with contrast-enhanced CT images. In this method, diagnosis stability and generalizability were improved through shape normalization based on anatomical structures as well as instance-level contrastive learning. Specifically, anatomically-guided shape normalization were developed to reconstruct the pancreatic regions of interest by spatial transformations, account for larger tumor parts in these regions, and hence enhance the extraction of pancreatic features. Moreover, instance-level contrastive learning was employed to aggregate different types of tumor features within the multiple instance learning framework. This learning approach can maintain the tumor feature integrity and enhance the diagnosis stability. Finally, a balance-adjustment strategy was designed to alleviate the class imbalance problem caused by the scarcity of tumor samples. Extensive experimental results demonstrated remarkable performance of our method when conducted cross-validation on an in-house dataset with 310 patients and independent test on two unseen datasets (a private test set with 316 and a publicly-available test set with 281). The proposed strategies also led to significant improvements in generalizability. Besides, the clinical significance of the proposed method was further verified through two independent test results in which tumors smaller than 2 cm in diameter were identified at accuracies of 80.9% and 90.1%, respectively. Overall, our method provides a potentially successful tool for early diagnosis of pancreatic cancer. Our source codes will be released at https://github.com/SJTUBME-QianLab/MIL_PAdiagnosis. [Display omitted] [ABSTRACT FROM AUTHOR]

The skin is the largest organ in humans. It comprises about 16% of our body. Many diseases originate from the skin, including acne vulgaris, skin cancer, fungal skin disease, etc. As a common skin cancer in China, melanoma alone grows at year rate of nearly 4%. Therefore, it is crucial to develop an objective, reliable, accurate, non-invasive, and easy-to-use diagnostic method for skin diseases to support clinical decision-making. Raman spectroscopy is a highly specific imaging technique, which is sensitive, even to the single-cell level in skin diagnosis. Raman spectroscopy provides a pattern of signals with narrow bandwidths, making it a common and essential tool for researching individual characteristics of skin cells. Raman spectroscopy already has a number of clinical applications, including in thyroid, cervical and colorectal cancer. This review will introduce the advantages and recent developments in Raman spectroscopy, before focusing on the advances in skin diagnosis, including the advantages, methods, results, analysis, and notifications. Finally, we discuss the current limitations and future progress of Raman spectroscopy in the context of skin diagnosis. [ABSTRACT FROM AUTHOR]

• A causal intervention based automated method for generalized pancreatic cancer diagnosis. • A continuous image generation strategy and a pancreatic feature diversification method are proposed to simulate appearance potential variations on limited dataset and enrich the feature diversity. • A causal intervention strategy is developed for alleviating spurious correlations caused by appearance changes, enhance causal feature extraction, thereby solving the challenges of generalization. • Extensive experiments conducted on a multi-center dataset with more than 1000 subjects showed that the proposed method achieves remarkable generalization performance. Pancreatic cancer (PC) is a severely malignant cancer variant with high mortality. Since PC has no obvious symptoms, most PC patients are belatedly diagnosed at advanced disease stages. Recently, artificial intelligence (AI) approaches have demonstrated promising prospects for early diagnosis of pancreatic cancer. However, certain non-causal factors (such as intensity and texture appearance variations, also called confounders) tend to induce spurious correlation with PC diagnosis. This undermines the generalization performance and the clinical applicability of the AI-based PC diagnosis approaches. Therefore, we propose a causal intervention based automated method for pancreatic cancer diagnosis with contrast-enhanced computerized tomography (CT) images, where a confounding effects reduction scheme is developed for alleviating spurious correlations to achieve unbiased learning, thereby improving the generalization performance. Specifically, a continuous image generation strategy was developed to simulate wide variations of intensity differences caused by imaging heterogeneities, where Monte Carlo sampling is added to further enhance the continuity of simulated images. Then, to enhance the pancreatic texture variability, a texture diversification method was introduced in conjunction with gradient-based data augmentation. Finally, a causal intervention strategy was proposed to alleviate the adverse confounding effects by decoupling the causal and non-causal factors and combining them randomly. Extensive experiments showed remarkable diagnosis performance on a cross-validation dataset. Also, promising generalization performance with an average accuracy of 0.87 was attained on three independent test sets of a total of 782 subjects. Therefore, the proposed method shows high clinical feasibility and applicability for pancreatic cancer diagnosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Two‐photon photodynamic therapy (TP‐PDT), which utilizes near‐infrared light to excite photosensitizer via two‐photon excitation (TPE), is a promising modality in the treatment of deeply seated tumors or thick tumors. However, the TPE domain is much smaller than the tumor volume, significantly limiting the therapeutical outcomes of TP‐PDT. Here, a light‐sheet TPE system is designed and constructed using a cylindrical lens for highly efficient TP‐PDT. The light‐sheet TPE performance is characterized and optimized via theoretical analysis and experimental studies in solution, phantom, and tumor. The optimized excitation system can reach a large TPE domain of 2.6 × 2.7 × 0.09 mm in the tumor, which is not achievable using conventional TPE methods, enabling TPE and subsequently generated reactive oxygen species to cover the whole tumor under line‐scanning. Outstanding TP‐PDT therapeutic performance of 70% tumor growth inhibition rate is achieved under line‐scanned light‐sheet TPE, making the proposed light‐sheet excited TP‐PDT a potential therapeutic tool for future translational research. [ABSTRACT FROM AUTHOR]

In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment, which renders it a valuable tool for both scientific research and clinical applications. However, the conventional approach for improving classification accuracy often involves labeling cells with fluorescence, which can lead to potential phototoxicity. This study proposes a label-free in-vivo flow cytometry technique, called dynamic YOLOv4 (D-YOLOv4), which improves classification accuracy by integrating absorption intensity fluctuation modulation (AIFM) into YOLOv4 to demodulate the temporal features of moving red blood cells (RBCs) and platelets. Using zebrafish as an experimental model, the D-YOLOv4 method achieved average precisions (APs) of 0.90 for RBCs and 0.64 for thrombocytes (similar to platelets in mammals), resulting in an overall AP of 0.77. These scores notably surpass those attained by alternative network models, thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivo flow cytometry, which holds promise for diverse in-vivo cell classification applications. [ABSTRACT FROM AUTHOR]

Addresses the spatial and temporal contact requirements for T cell activation and minimum number of receptors that must be engaged to transmit a calcium signal. Cell culture; Antibody coating on beads; Optical trapping; Contact-area estimation; Discussion on T cell functional polarity identified with an optical trap.

Photodynamic therapy (PDT) takes advantage of photosensitizers (PSs) to generate reactive oxygen species (ROS) for cell killing when excited by light. It has been widely used in clinic for therapy of multiple cancers. Currently, all the FDA-approved PSs, including porphyrin, are all small organic molecules, suffering from aggregation-caused quenching (ACQ) issues in biological environment and lacking tumor targeting capability. Nanoparticles (NPs) with size between 20 nm and 200 nm possess tumor targeting capability due to the enhanced permeability and retention (EPR) effect. It is urgent to develop a new strategy to form clinical-approved-PSs-based NPs with improved ROS generation capability. In this study, we report a strategy to overwhelm the ACQ of porphyrin by doping it with a type of aggregation-induced emission (AIE) luminogen to produce a binary NPs with high biocompatibility, and enhanced fluorescence and ROS generation capability. Such NPs can be readily synthesized by mixing a porphyrin derivative, Ce6 with a typical AIE luminogen, TPE-Br. Here, our experimental results have demonstrated the feasibility and effectiveness of this strategy, endowing it a great potential in clinical applications. [ABSTRACT FROM AUTHOR]

The controlled rotation of individual cells plays a crucial role in enabling three-dimensional multi-angle observation of cellular structure, function, and dynamic processes. Reported cell rotation techniques often struggle to strike a balance between high precision and simple control, and they exhibit limited control flexibility, typically achieving only uniaxial cell rotation. In this study, we propose a cell rotation technique in three dimensions based on optofluidics, which utilizes optical tweezers to immobilize the cell and exploits the asymmetry of the surrounding flow to drive cell rotation. By adjusting the focal position of the optical tweezers, cells can be positioned within various flow profiles, enabling control of the rotation speed, rotation direction, and rotation axis of cells. This approach simplifies the manipulation procedure, achieving desirable control precision and greater rotation flexibility. Using our approach, multi-angle surface imaging projections of target cells can be rapidly obtained, followed by capturing the cell contour data from the images. By combining the cell contour data with corresponding angular position information, we have reconstructed the 3D surface of the target cell. We have employed this technique in experiments for the analysis of red blood cell morphology. Based on the constructed 3D surface images of diverse-shaped red blood cells, we quantified structural parameters including cell surface area, volume, sphericity, and surface roughness, which demonstrates the potential application of this cell rotation technique for cellular morphological analysis. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) has received widespread attention due to its selectivity and oxygen independence, and is an emerging therapeutic methodology aimed at converting hydrogen peroxide (H2O2) into hydroxyl radicals (˙OH). Despite the overexpression of H2O2 in solid tumors, the content is too low for efficient CDT. Here, the integration of H2O2 self-supply and photothermal response was achieved using the synthesized nanoparticles, which are CuS/CaO2@PCM (phase change material) nanoparticles. After NIR irradiation, the thermo-responsive PCM was melted to precisely release CuS and CaO2 from nanoparticles. In response to the acidic tumor microenvironment (TME), CaO2 can produce a large amount of H2O2 to participate in a Fenton-like reaction. In turn, the generated ˙OH induces a series of oxidative damage that triggers apoptosis. Meanwhile, CuS converts photon energy into heat via photothermal therapy (PTT) to enhance the antitumor effect. The in vitro and in vivo therapeutic outcomes demonstrated that CuS/CaO2@PCM nanoparticles efficiently generate toxic H2O2 and hyperthermia at the tumor site, thus enabling enhanced CDT and PTT effects. This therapeutic strategy offers a self-amplified synergistic treatment paradigm for tumors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the overall sensitivity and specificity of indocyanine green (ICG)-near-infrared (NIR) fluorescence imaging in the detection of sentinel lymph node metastasis (SLNM) in penile cancer. Methods: We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases to identify manuscripts where ICG was intravenously administered prior to or during penile cancer surgery, with no restriction on language or publication status. The results extracted are presented as forest plots. Results: Seven studies were included in the analysis. The median sensitivity and specificity of ICG-NIR imaging for SLNM detection were 100 and 4%, respectively; the pooled sensitivity was 100.0% (95% confidence interval [CI] 97.0–100.0) and specificity was 2.0% (95% CI 1.0–3.0). There was no significant difference in the diagnostic results between different injection sites and doses in each experimental group. Conclusion: To our knowledge, this meta-analysis is the first to summarize the diagnostic performance of ICG-NIR imaging for SLNM detection in penile cancer. ICG is sensitive in the imaging of SLN tissue, which can consequently improve the accuracy of lymph node detection. However, the specificity is very low. [ABSTRACT FROM AUTHOR]

Soluble CD83 (sCD83) exerts immunosuppressive functions in many autoimmune diseases, including experimental autoimmune uveitis (EAU), but the cells and mechanisms involved are unclear. This study showed that CD83+ B cells were the main sources of sCD83. They alleviated the symptoms of EAU and decreased the percentage of T cells and DCs in the eyes and lymph nodes. These CD83+ B cells decreased IL‐1β, IL‐18 and IFN‐γ secretion by DCs through sCD83. sCD83 interacted with GTPase Ras‐related protein (Rab1a) in DCs to promote Rab1a accumulation in autolysosomes and inhibit mTORC1 phosphorylation and NLRP3 expression. Hence, CD83+ B cells play a regulatory role in EAU by secreting sCD83. The lack of regulation of CD83+ B cells might be an important factor leading to hyperimmune activation in patients with autoimmune uveitis. CD83+ B cells suppress activated DCs in uveitis, indicating the potential therapeutic role of CD83+ B cells in uveitis. [ABSTRACT FROM AUTHOR]

Optical tweezers are ideal tools for cell manipulation in vivo due to their non-contact trapping ability. In the current studies, the optical trapping of cells can only be achieved in light-permeable organs. It is important to expand the application of optical tweezers to opaque tissues and organs, where biological activities are the primary focus of biomedical research. However, the optical manipulation of cells in these opaque organs cannot be imaged using a conventional transillumination microscope due to the opacity of these organs. Here, we use optical tweezers to trap erythrocytes and measure the cell deformability in mouse liver, which are imaged with oblique back-illumination microscopy (OBM). In the microscope system, two fibers are fixed at the same oblique angle on both sides of the microscopic objective, illuminating the trapping target asymmetrically. The dual-wavelength OBM strategy allows for obtaining a differential phase contrast image in a single-shot by color channel separation. The OBM can image the flowing and trapped erythrocytes in vivo in real-time. Furthermore, the erythrocyte deformability in vivo is evaluated with optical tweezers. The spring stiffness in vivo is 8.2 ± 2.1 μN m−1, which is obtained by stretching the trapped cells with blood drag flow. Our works make it possible to utilize optical tweezers to study the live cell dynamics in opaque organs, which will expand the application of optical tweezers in the fields of biomechanical studies. [ABSTRACT FROM AUTHOR]

The study of circulating cells in the blood stream is critical, as it covers many fields of biomedicine, including immunology, cell biology, oncology, and reproductive medicine. In-vivo flow cytometry (IVFC) is a new tool to monitor and count cells in real time for long durations in their native biological environment. This review describes two main categories of IVFC, i.e., labeled and label-free IVFC. It focuses on label-free IVFC and introduces its technological development and related biological applications. Because cell recognition is the basis of flow cytometry counting, this review also describes various methods for the classification of unlabeled cells, including the latest machine learning-based technologies. [ABSTRACT FROM AUTHOR]

In the traditional two-step procedure used in intensity-modulated radiation therapy, fluence map optimization (FMO) is performed first, followed by use of a leaf sequencing algorithm (LSA). By contrast, direct aperture optimization (DAO) directly optimizes aperture leaf positions and weights. However, dose calculation using the Monte Carlo (MC) method for DAO is often time-consuming. Therefore, a rapid DAO (RDAO) algorithm is proposed that uses a dose influence matrix based piecewise aperture dose model (DIM-PADM). In the proposed RDAO algorithm, dose calculation is based on the dose influence matrix instead of MC. The dose dependence of aperture leafs is modeled as a piecewise function using the DIM. The corresponding DIM-PADM-based DAO problem is solved using a simulated annealing algorithm.The proposed algorithm was validated through application to TG119, prostate, liver, and head and neck (H&N) cases from the common optimization for radiation therapy dataset. Compared with the two-step FMO–LSA procedure, the proposed algorithm resulted in more precise dose conformality in all four cases. Specifically, for the H&N dataset, the cost value for the planned target volume (PTV) was decreased by 32%, whereas the cost value for the two organs at risk (OARs) was decreased by 60% and 92%. Our study of the proposed novel DIM-PADM-based RDAO algorithm makes two main contributions: First, we validate the use of the proposed algorithm, in contrast to the FMO–LSA framework, for direct optimization of aperture leaf positions and show that this method results in more precise dose conformality. Second, we demonstrate that compared to MC, the DIM-PADM-based method significantly reduces the computational time required for DAO. [ABSTRACT FROM AUTHOR]

Malignant breast cancer (BC) remains incurable mainly due to the cancer cell metastasis, which is mostly related to the status of Estrogen receptor alpha (ERα). However, our understanding of the mechanisms through which ERα regulates cancer cell metastasis remains limited. Here we identified a miR-29a-PTEN-AKT axis as a downstream signaling pathway of ERα governing breast cancer progression and metastasis. Two estrogen response element (ERE) half sites were identified in the promoter and enhancer regions of miR-29a, which mediated transcriptional regulation of miR-29a by ERα. Low level of miR-29a showed association with reduced metastasis and better survival in ERα+ luminal subtype of BC. In contrast, high level of miR-29a was detected in ERα- triple negative breast cancer (TNBC) in association with distant metastasis and poor survival. miR-29a overexpression in BC tumors increased the number of circulating tumor cells and promoted lung metastasis in mice. Targeted knockdown of miR-29a in TNBC cells in vitro or administration of a nanotechnology-based anti-miR-29a delivery in TNBC tumor-bearing mice in vivo suppressed cellular invasion, EMT and lung metastasis. PTEN was identified as a direct target of miR-29a, inducing EMT and metastasis via AKT signaling. A small molecular inhibitor of AKT attenuated miR-29a-induced EMT. These findings demonstrate a novel mechanism responsible for ERα-regulated breast cancer metastasis, and reveal the combination of ERα status and miR-29a levels as a new risk indicator in BC. [ABSTRACT FROM AUTHOR]

Background: Laboratory investigations have demonstrated that near-infrared (NIR) light treatment can reduce amyloid-β burden in models of Alzheimer's disease (AD). However, previous clinical studies are rather insufficient.Objective: Before starting a large-scale clinical trial, we performed a pilot study to characterize the efficacy of NIR light for AD patients.Methods: Twenty participants with mild to moderate AD were assigned randomly to the intervention (1060-1080 nm and 800-820 nm NIR light treatment for 12 weeks) or control group (without sham treatment). Safety and efficacy were evaluated at baseline, week 4, 8, and 12, and 4 weeks after treatment.Results: In the intervention and control groups at week 12, mean changes from baseline on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) were -3.1 and -1.3 (p = 0.5689). Mean changes from baseline on the Activities of Daily Living (ADL) were -3.6 versus 3.1 (p = 0.0437). Mean changes from baseline on the Mini-Mental State Examination (MMSE) were 4.4 versus 1.0 (p = 0.0253). The percentage of participants who exhibited a change larger than 4 points from baseline to week 12 was determined for the intervention and control groups on the ADAS-Cog (57% versus 29%), ADL (29% versus 0%), and MMSE (57% versus 14%). Treatment with NIR light did not increase the incidence of adverse events in participants.Conclusion: NIR light treatment appears to be safe and potentially beneficial for AD patients. It improved cognitive function and activities of daily living. The preliminary data encouraged us to launch a large-sample, multicenter, double-blind clinical trial. [ABSTRACT FROM AUTHOR]

We propose a novel retinal layer segmentation method to accurately segment 10 retinal layers in optical coherence tomography (OCT) images with intraretinal fluid. The method used a fan filter to enhance the linear information pertaining to retinal boundaries in an OCT image by reducing the effect of vessel shadows and fluid regions. A random forest classifier was employed to predict the location of the boundaries. Two novel methods of boundary redirection (SR) and similarity correction (SC) were combined to carry out boundary tracking and thereby accurately locate retinal layer boundaries. Experiments were performed on healthy controls and subjects with diabetic macular edema (DME). The proposed method required an average of 415 s for healthy controls and of 482 s for subjects with DME and achieved high accuracy for both groups of subjects. The proposed method requires a shorter running time than previous methods and also provides high accuracy. Thus, the proposed method may be a better choice for small training datasets. [ABSTRACT FROM AUTHOR]

NADH shuttles mediate the transfer of the reducing equivalents of cytosolic NADH into mitochondria. Cumulating evidence has suggested that malate-aspartate shuttle (MAS), one of the two types of NADH shuttles, plays significant roles in such biological processes as glutamate synthesis in neurons. However, there has been no information regarding the roles of NADH shuttle in the survival and energy metabolism of microglia. In current study, using microglial BV2 cells as a cellular model, we determined the roles of MAS in the survival and energy metabolism of microglia by using aminooxyacetate acid (AOAA)-a widely used MAS inhibitor. Our study has suggested that AOAA can effectively inhibit the MAS activity of the cells. We also found that AOAA can induce both early- and late-stage apoptosis of resting microglia and lipopolysaccharides (LPS)-activated microglia. AOAA also induced mitochondrial depolarization, increases in the cytosolic Ca concentrations, and decreases in the intracellular ATP levels. Moreover, our study has excluded the possibility that the major nonspecific effect of AOAA-inhibition of GABA transaminase-is involved in theses effects of AOAA. Collectively, our study has provided first information suggesting significant roles of MAS in the survival and energy metabolism in both resting microglia and LPS-activated microglia. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD) plays critical roles in energy metabolism, mitochondrial functions, calcium homeostasis and immunological functions. Our previous studies have found that NAD administration can profoundly decrease ischemic brain injury and traumatic brain injury. Our recent study has also provided first direct evidence indicating that NAD treatment can decrease cellular apoptosis, while the mechanisms underlying this protective effect remain unclear. In our current study, we determined the effects of NAD treatment on several major factors in apoptosis and necrosis, including levels of Bax and nuclear translocation of apoptosis-inducing factor (AIF), as well as levels of DNA double-strand breaks (DSBs) and intracellular ATP in rotenone-treated differentiated PC12 cells. We found that NAD treatment can markedly attenuate the rotenone-induced increases in the levels of Bax and nuclear translocation of AIF in the cells. We further found that NAD treatment can significantly attenuate the rotenone-induced increase in the levels of DSBs and decrease in the intracellular ATP levels. Collectively, our study has suggested mechanisms underlying the preventive effects of NAD on apoptosis, which has highlighted the therapeutic potential of NAD for decreasing apoptotic changes in multiple major diseases. [ABSTRACT FROM AUTHOR]

Terahertz metamaterial sensing (TMS) is a new interdisciplinary technology. A TMS system employs terahertz waves as the pumping source, these then interact with the sample and carry the substance information, e.g., refractive index, absorption spectra. These properties are relevant to the molecular rotation and vibration states produced by a surface‐plasmon‐polariton‐like effect. TMS technology is usually characterized by large penetration depth and high sensitivity. Owing to these advantages, TMS may be used for ultratrace detection and consequently has a wide range of practical applications in biomedicine, food safety, environmental monitoring, industry and agriculture, material characterization, and safety inspection. Furthermore, TMS performance is determined not only by the structural topology of metamaterials, but also by their compositions and substrates. This paper reviews the essential fundamentals, relevant applications, and recent advances in TMS technology with a focus on the influence of material selection on TMS performance. This review is envisaged to be used as a key reference for developing TMS‐based functional devices with enhanced characteristics. [ABSTRACT FROM AUTHOR]

Refractive surgery is recognized as an effective method for myopia treatment, but it can induce night vision disturbances such as glare. We present an eye modeling method for the optical quality assessment in response to the structural changes in the eyes by femto-LASIK surgery. Customized eye models were built from the measurements of 134 right eyes pre- and post-operatively. Optical performance was evaluated using spot diagrams, point spread functions (PSFs), modulation transfer functions (MTFs), and chromatic aberrations at various fields (0°–30°), different pupil diameters (2–6 mm), and initial myopias (− 1.25 to − 10.5 D). Pupil size and initial myopia are the two major factors that affect visual performance of post-operative eyes. The results of spot diagrams, PSFs, and MTFs indicated that post-operative visual performance deteriorated as the visual field and pupil size increased, and it was significantly influenced by initial myopia. Post-operative chromatic aberrations were also affected by initial myopia. As pupil size increased, the post-operative longitudinal chromatic aberrations tended to decrease slightly, while the transverse chromatic aberrations remained similar. The use of eye modeling for refractive surgery assessment could possibly provide a more personalized surgical approach, could improve the prediction accuracy of refractive surgery outcomes, and promote the invention and development of better surgical methods. [ABSTRACT FROM AUTHOR]

Developing a high-resolution non-invasive optical coherence tomography angiography (OCTA) method for iris vasculature imaging is essential for diagnosing a wide range of ocular pathologies. However, the current iris-OCTA devices are still limited in imaging quality and penetration depth for dark-colored eyes ranging from brown to dark brown. A spectral domain iris-OCTA system is presented in this paper incorporating a 1300 nm wavelength for deeper tissue penetration, a linear-wavenumber spectrometer for better detection sensitivity, and an iris scan objective lens for better optical focusing across the entire iris over a 12 × 12 mm2 scan field. The −6 dB fall-off range is ∼3 mm, and the maximum sensitivity fall-off is −28.57 dB at 6.94 mm. The axial resolution is 15.1 ± 3.2 μm. The 40 mm focal-length iris scan objective is optimized based on the ocular parameters from 100 Asian participants' left eyes, and it has a diffraction-limited lateral resolution (14.14 μm) for the iris, in general. OCT distortions were calibrated based on the average ocular parameters, and the maximum residual distortions in both the lateral and axial directions were <0.1 mm (2.0%) for all of the eyes. A pilot study on a constricted pupil was performed to demonstrate high-contrast, wide-field en face iris microvascular imaging by either a horizontal or vertical fast-scan protocol in a dark brown eye. The iris vessels are radially aligned, and each vessel is more visible when it has an angle of ∼65°–90° with respect to the fast-scan direction. A new circular fast-scan protocol could improve image quality for better visualization of the iris features or integration with image-registration algorithms and an eye-tracking system for eye-motion compensation. [ABSTRACT FROM AUTHOR]

Abstract: To develop an apparatus for simultaneous monitoring of heart and respiratory rates using photoplethysmography (PPG) and Fast Fourier Transform algorithm (FFT), the PPG waveform was measured at the radial artery with an original based on diffuse reflectance mode photoplethysmographic device. An FFT algorithm was used to extract heart and respiratory information from the PPG waveform. The results good agree with conventional method. The correlation coefficient of heart rate and respiratory rate obtained using PPG waveform and conventional method is 0.988 and 0.976, respectively. The PPG waveform and FFT algorithm can contribute to quicker and more accurate measurement of human heart rate and respiration rate. A portable watch-like device can be made via this method and be utilized to monitor heart and respiratory rates in hospitals or daily life care. [Copyright &y& Elsevier]

Patient-derived organoids (PDOs) closely recapitulate human colorectal cancer biology and have recently emerged as preclinical models for personalized therapy design.1 However, PDOs cultured in Matrigel (PDOs SP Matrigel sp ) failed to predict outcome for treatment with the first-line FO chemotherapeutic regimen (5-fluorouracil plus oxaliplatin) for metastatic colorectal cancer (mCRC) patients.2 In this study, we establish in vitro culture conditions of mCRC-PDOs in a hydroxypropyl cellulose allyl conjugated with collagen (HA-Coll sponge),3 and utilized this system to examine the drug sensitivity of FO regimen (Figure 1A). PDOs in HA-Coll sponge (PDOs SP Sponge sp ) proliferated at the same level as PDOs SP Matrigel sp in the next generation (Figure 2B and C, Figure S1C and D). Conclusively, our results indicated that PDOs SP Sponge sp remained the original epithelial state of parental tumor tissues, which is important for the drug-sensitivity of FO, but not for irinotecan. To further confirm these results, we knocked out I LMNA i in PDOs SP Sponge sp and overexpressed I LMNA i in PDOs SP Matrigel sp to perform the drug response assay. [Extracted from the article]

We welcome the readers to the special issue on single cell analysis (Part II), which highlights recent progress in the development of single-cell optical analysis techniques and their applications in biological discovery, disease diagnosis, and treatment. Coherent Raman scattering (CRS) microscopy is capable of chemically selective, highly sensitive, submicron resolution, and high-speed imaging of lipid molecules in single live cells without any labeling. Raman spectroscopy is a highly specific imaging technique, which is sensitive, even to the single-cell level in skin diagnosis. [Extracted from the article]

With the rapid growth of anti-terrorist activities worldwide, it becomes an emerging requirement to rapidly and accurately detect hidden explosive threats. However, the safety issue during the explosive material detection, e.g. unexpected explosion, is still an insurmountable challenge. In this study, we design and mass-produce a novel kind of flexible 5,10,15,20-tetrakis(4-aminophenyl)porphyrin doped polymer optical fiber (PPOF) for rapid and accurate detection of trace 2,4-dinitrotoluene (DNT) vapor based on the DNT induced florescence quenching mechanism. The influence of doping concentration, bending, and temperature on the sensing performance is investigated. PPOF shows immunity to bending, enabling it to work in a harsh environment. It is experimentally demonstrated that the limit of detection and response time of the proposed PPOF could reach around 120 ppb and 3 minutes, respectively, which make it much better than other techniques. Owning to its inherent advantages including low-cost, remote-control capability, and compatibility with optical communication networking, PPOF can be constructed the quasi-distributed sensing networking of explosive matters in the future, providing a new strategy for anti-terrorism. [ABSTRACT FROM AUTHOR]

The elaboration of nanotechnology offers valuable therapeutic options to overcome the blood-brain barrier and enable the treatment of brain diseases. However, to date, limit work has been done to reveal the fate of nanoparticles within the brain, which largely hinders their safe and effective applications. Here we demonstrated that the commonly-used organic nanoparticles reconstituted high density lipoprotein and poly(ethylene glycol)-b-poly(lactic acid) nanoparticles were cleared relatively fast from the brain (half-life <5 h). Notably, through various transgenic mice and pharmacological inhibition approaches, we revealed that the paravascular glymphatic pathway plays a key role (about 80%) in the brain clearance of the nanoparticles, and disclosed that microglia-mediated transportation is essential for facilitating nanoparticles elimination through the paravascular route. In addition, we witnessed a significant decline in the brain clearance of both of the nanoparticles in Alzheimer's model mice where the glymphatic system is impaired. These findings provide insightful data on the fate of nanoparticles in the brain, which would shed new light into the rational design and safe application of nanoparticles for brain drug delivery. The rHDL and PEG-PLA nanoparticles in the brain are majorly transported through microglia to the paravascular glymphatic pathway, the major route for their brain elimination. Unlabelled Image • rHDL and PEG-PLA nanoparticles were cleared relatively fast from the brain. • Paravascular glymphatic pathway is the major route for brain elimination of the nanoparticles. • Microglia facilitates nanoparticles transport to the paravascular route. • Brain clearance of the nanoparticles was significantly declined under Alzheimer condition. [ABSTRACT FROM AUTHOR]

The fluorescence-based in vivo flow cytometry (IVFC) is an emerging tool to monitor circulating cells in vivo. As a noninvasive and real-time diagnostic technology, the fluorescence-based IVFC allows long-term monitoring of circulating cells without changing their native biological environment. It has been applied for various biological applications (e.g., monitoring circulating tumor cells). In this work, we will review our recent works on fluorescence-based IVFC. The operation principle and typical biological applications will be introduced. In addition, the recent advances in IVFC flow cytometry based on photoacoustic effects and other label-free detection methods such as imaging-based methods, diffuse-light methods, hybrid multimodality methods and multispectral methods are also summarized. [ABSTRACT FROM AUTHOR]

Due to the high mobility of copper ions in numerous structurally-related phases, copper sulphide (Cu2−xS, 0 ≤ x ≤ 1) has been widely used as a starting template to fabricate various heterostructures via cation exchange. Such nanoheterostructures can possess unique combinations of physical properties that could be useful in diverse applications. Controllable methods of fabricating copper sulphide nanoheterostructures of increasing complexity have been rapidly emerging over the past few years. In this tutorial review, we discuss recent progress in heterostructure fabrication methods using copper sulphide. We primarily focus on important reports of cation exchange-based approaches and then summarize some key emerging applications that can employ these copper-sulphide-based nanoheterostructures. [ABSTRACT FROM AUTHOR]

Objective: Visualizing cell interactions in blood circulation is of great importance in studies of anticancer immunotherapy or drugs. However, the lack of a suitable imaging system hampers progress in this field. Methods: In this work, we built a dual-channel in vivo imaging flow cytometer to visualize the interactions of circulating tumor cells (CTCs) and dendritic cells (DCs) simultaneously in the bloodstream. Two artificial neural networks were trained to identify blood vessels and cells in the acquired images. Results and Conclusion: Using this technique, single CTCs and CTC clusters were readily distinguished by their morphology. Interactions of CTCs and DCs were identified, while their moving velocities were analyzed. The CTC-DC clusters moved at a slower velocity than that of single CTCs or DCs. This may provide new insights into tumor metastasis and blood rheology. Significance: This in vivo imaging flow cytometry system holds great potential for assessing the efficiency of targeting CTCs with anticancer immune cells or drugs. [ABSTRACT FROM AUTHOR]

Shutong Liu et al. proposed a new feature extraction method in fluorescence imaging of nucleus to achieve automatic and accurate identification of apoptosis with low cost in terms of time,[4] which may facilitate large-scale single-cell analysis. Therefore, it is crucial to develop novel single cell analysis techniques, including spectroscopy, imaging, sensing, manipulating, and sorting. Increasing evidence has shown that cell populations are not homogeneous, but rather heterogeneous, even within very small cell populations. [Extracted from the article]

Recent studies in oncology have addressed the importance of detecting circulating tumor cell clusters because circulating tumor cell clusters might survive and metastasize more easily than single circulating tumor cells. Signals with larger peak widths detected by in vivo flow cytometer (IVFC) have been used to identify cell clusters in previous studies. However, the accuracy of this criterion might be greatly degraded by variance in blood flow and the rolling behaviors of circulating tumor cells. Here, we propose a criterion and algorithm to distinguish cell clusters from single cells. In this work, we first used area-based and volume-based models for single fluorescent cells. Simulating each model, we analyzed the corresponding morphology of IVFC signals from cell clusters. According to the Rayleigh criterion, the valley between two adjacent peak signals from two distinguishable cells should be lower than 73.5% of the peak values. A novel signal processing algorithm for IVFC was developed based on this criterion. The results showed that cell clusters can be reliably identified using our proposed algorithm. Intravital imaging was also performed to further support our algorithm. With enhanced accuracy, IVFC is a powerful tool to study circulating cell clusters. [ABSTRACT FROM AUTHOR]

Two-photon microscopy (TPM) has been one of the most widely used fluorescent microscopy methods in biological tissue. The femtosecond laser in the near-infrared (NIR) range showed better penetration in tissue due to less scattering and absorption. The method to estimate the optimal wavelength generally according to the scattering and absorption is somehow too rough considering the complex biological property and other factors that influence TPM. In this report, we set up a model to calculate the optimal wavelength in the NIR range for different imaging depths by involving more parameters of TPM. The calculated result suggests the image of brain slice stained with fluorescein isothiocyanate (FITC) can be acquired with the best TPM imaging quality at 780 nm excitation rather than longer wavelengths, which is consistent with our experimental results of TPM at depth of 50-300 μm in mouse brain tissue. Our results may, therefore, bring a better understanding on TPM in tissue and help to develop a more accurate model for the simulation of TPM. [ABSTRACT FROM AUTHOR]

Nanoparticles have been widely used in biomedical research as drug carriers or imaging agents for living animals. Blood circulation is crucial for the delivery of nanoparticles, which enter the bloodstream through injection, inhalation, or dermal exposure. However, the clearance kinetics of nanoparticles in blood circulation has been poorly studied, mainly because of the limitations of conventional detection methods, such as insufficient blood sample volumes or low spatial-temporal resolution. In addition, formation of nanoparticle aggregates is a key determinant for biocompatibility and drug delivery efficiency. Aggregation behavior of nanoparticles in blood is studied using dynamic light scattering in serum or serum protein solutions, which is still very different from in vivo condition. In this work, we monitored the dynamics of nanoparticle concentration and formation of nanoparticle aggregates in the bloodstream in live animals using in vivo flow cytometry (IVFC). The results indicated that nanoparticles in smaller size could stay longer in the bloodstream. Polyethylene glycol (PEG)-modification could prolong circulating time and reduce the formation of aggregates in the blood circulation. Our work shows that IVFC can be a powerful tool for pharmacokinetic studies of nanoparticles and other drug carriers, assessing cell-targeting efficiency, as well as potentially measuring cardiac output and hepatic function in vivo . [ABSTRACT FROM AUTHOR]

T-cell activation requires the formation of the immunological synapse (IS) between a T-cell and an antigen-presenting cell (APC) to control the development of the adaptive immune response. However, calcium release, an initial signal of T-cell activation, has been found to occur before IS formation. The mechanism for triggering the calcium signaling and relationship between calcium release and IS formation remains unclear. Herein, using live-cell imaging, we found that intercellular adhesion molecule 1 (ICAM-1), an essential molecule for IS formation, accumulated and then was depleted at the center of the synapse before complete IS formation. During the process of ICAM-1 depletion, calcium was released. If ICAM-1 failed to be depleted from the center of the synapse, the sustained calcium signaling could not be induced. Moreover, depletion of ICAM-1 in ISs preferentially occurred with the contact of antigen-specific T-cells and dendritic cells (DCs). Blocking the binding of ICAM-1 and lymphocyte function-associated antigen 1 (LFA-1), ICAM-1 failed to deplete at the center of the synapse, and calcium release in T-cells decreased. In studying the mechanism of how the depletion of ICAM-1 could influence calcium release in T-cells, we found that the movement of ICAM-1 was associated with the localization of LFA-1 in the IS, which affected the localization of calcium microdomains, ORAI1 and mitochondria in IS. Therefore, the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sustained calcium release in T-cells. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disease. The symptoms include memory and spatial learning difficulties, language disorders, and loss of motivation, which get worse over time, eventually ending in death. No effective treatments are available for AD, currently. Current treatments only attenuate symptoms temporarily and are associated with severe side effects. Near infra-red (NIR) light has been studied for a long time. We investigated the effect of NIR on AD using a transgenic mouse model, which was obtained by co-injecting two vectors carrying AD mutations in amyloid precursor protein (APP) and presenilin-1 (PSEN1) into C57BL/6J mice. The irradiation equipment consisted of an accommodating box and an LED array. The wavelength of NIR light emitted from LED was between 1040nm and 1090nm. The power density delivered at the level of the mice was approximately 15mW/cm2. Firstly, we treated the mice with NIR for 40 days. Then, the irradiation was suspended for 28 days. Finally, another 15 days treatment was brought to mice. We conducted Morris water maze and immunofluorescence analysis to evaluate the effects of treatment. Immunofluorescence analysis was based on measuring the quantity of plaques in mouse brain slices. Our results show that NIR light improves memory and spatial learning ability and reduces plaques moderately. NIR light represents a potential treatment for AD. [ABSTRACT FROM AUTHOR]

In biomedical research fields, the in vivo flow cytometry (IVFC) is a widely used technology which is able to monitor target cells dynamically in living animals. Although the setup of IVFC system has been well established, baseline drift is still a challenge in the process of quantifying circulating cells. Previous methods, i.e., the dynamic peak picking method, counted cells by setting a static threshold without considering the baseline drift, leading to an inaccurate cell quantification. Here, we developed a method of cell counting for IVFC data with baseline drift by interpolation fitting, automatic segmentation and wavelet-based denoising. We demonstrated its performance for IVFC signals with three types of representative baseline drift. Compared with non-baseline-correction methods, this method showed a higher sensitivity and specificity, as well as a better result in the Pearson's correlation coefficient and the mean-squared error (MSE). [ABSTRACT FROM AUTHOR]

Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as ‘seeds’. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect. Enhanced cellular uptake, cell apoptosis-induction and cell-viability inhibition efficiency of the peptide and aptamer dual-functionalized nanoparticles (dTNP) were observed in both human umbilical vein endothelial cells (HUVEC) and 4T1 cells in vitro . Using cone-and-plate viscometer to create venous flow velocity, dTNP was also found to be able to capture CTCs under shear stress. The CTC-targeting and neutralization effect of dTNP in bloodstream and 4T1-GFP cell-derived lung metastasis mice model was confirmed via in vivo flow cytometry (IVFC), intravital imaging and confocal microscopy analysis. As a result, the orthotropic breast tumor-bearing mice administrated with PTX-loaded dTNP exhibited the optimal therapeutic effect. Taken together, the findings here provided direct evidence that the tumor neovasculature and CTCs dual-targeting drug delivery system could provide a novel modality for the treatment of highly-invasive breast cancer. [ABSTRACT FROM AUTHOR]

NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures. AOAA also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells. Moreover, the toxic effects of AOAA were completely prevented by pyruvate treatment. Collectively, our study has suggested that AOAA may be used to selectively decrease glioma cell survival, and the major function of MAS in cancer cells may be profoundly different from its major function in normal cells: The major function of MAS in cancer cells is to maintain glycolysis, instead of increasing mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By studying NADH-treated differentiated PC12 cells, we found that NADH induced a significant increase in the nuclear Nrf2, which was prevented by both SIRT2 si RNA and SIRT2 inhibitor, AGK2. SIRT2 si RNA also blocked the NADH-induced increases in glutamate cysteine ligase ( GCL) and glutathione. Moreover, SIRT2 si RNA and AGK2 blocked NADH-induced Akt phosphorylation, and inhibition of Akt phosphorylation prevented NADH-induced increases in the nuclear Nrf2 and glutathione. Collectively, our study shows that SIRT2 regulates nuclear Nrf2 levels by modulating Akt phosphorylation, thus modulating the levels of GCL and total glutathione. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been commonly used in treating many diseases, such as cancer and infectious diseases. We investigated the different effects of PDT on three main pathogenic bacteria of periodontitis - Prevotella melaninogenica (P.m.), Porphyromonas gingivalis (P.g.) and Aggregatibacter actinomycetemcomitans (A.a.). The portable red light-emitting diode (LED) phototherapy device was used to assess the exogenous PDT effects with different light doses and photosensitizer concentrations (Toluidine blue O, TBO). The portable blue LED phototherapy device was used to assess the endogenous PDT effects with the use of endogenous photosensitizers (porphyrin) under different light doses. We found out that both exogenous and endogenous PDT were able to restrict the growth of all the three bacteria significantly. Moreover, the optimal PDT conditions for these bacteria were obtained through this in vitro screening and could guide the clinical PDT on periodontitis. [ABSTRACT FROM AUTHOR]

The immunological synapse (IS) is a supermolecular activation cluster formed between T cells and antigen-presenting cells. Although diverse IS structures have been reported, the function of the IS in T-cell activation remains unclear. Here, we found that the bullseye IS, one of IS types at the interface of CD4+ T cells and staphylococcal enterotoxin B-pulsed dendritic cells, suppressed CD4+ T-cell activation, whereas multifocal IS, another synapse type, stimulated CD4+ T-cell activation. Consistent with these results, bullseye IS formation was accompanied by a low-level calcium response in T cells and a loss of T-cell receptor signalling molecules from the synapse, whereas multifocal IS exhibited the opposite. Furthermore, we found that CD4+ CD25+ regulatory T cells (Tregs) more efficiently formed bullseye IS and promoted bullseye IS formation in CD4+ CD25- T cells. Cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule expressed continuously on Tregs, was localised in bullseye IS. Moreover, blocking CTLA-4 reduced the percentage of bullseye IS formation and promoted T-cell activation. Our data thus indicate that bullseye IS formation is mediated by CTLA-4, and may negatively control T-cell activation as a suppressive synapse. [ABSTRACT FROM AUTHOR]

Highlights: [•] NAD+ treatment can decrease rotenone-induced early-stage and late-stage apoptosis of PC12 cells. [•] NAD+ treatment can decrease rotenone-induced necrosis of PC12 cells. [•] NAD+ treatment can restore the intracellular NAD+ levels of rotenone-treated PC12 cells. [•] NAD+ treatment can prevent rotenone-induced mitochondrial depolarization of PC12 cells. [Copyright &y& Elsevier]

Highlights: [•] The SIRT2 inhibitor AGK2 can induce both late-stage apoptosis and necrosis of microglial BV2 cells. [•] The SIRT2 inhibitor AGK2 can induce a decrease in the intracellular ATP levels of microglial BV2 cells. [•] Poly(ADP-ribose) polymerase activation mediates both the cell death and the ATP decline of AGK2-treated microglial BV2 cells. [ABSTRACT FROM AUTHOR]

Abstract: We report, for the first time to our knowledge, on the application of a micro-optical lens fabricated by three-dimensional (3D) femtosecond laser direct writing for two-photon fluorescence imaging of biological tissues. We show that the two-photon fluorescence images of a plant leaf tissue acquired with the micro-optical lens are comparable to that of a 5× objective lens. Our result represents an important step towards the application of micro-optical components fabricated by femtosecond laser micromachining in miniaturized nonlinear fluorescence microscopy applications, such as two-photon endoscopy. [Copyright &y& Elsevier]

Abstract: Confocal fluorescence imaging and fluorescence resonance energy transfer (FRET) technology have been widely used to study protein–protein interactions in living cells. However, it is very difficult to quantitatively analyze FRET efficiency due to the excitation spectral crosstalk and emission spectral crosstalk between donor and acceptor. In this study, we developed a novel method to quantitatively obtain the FRET efficiency by fitting the emission spectra (FES) of donor–acceptor pair, and this method is free from both excitation and emission spectral crosstalk. We used the FES method to quantitatively monitor the FRET efficiency of SCAT3, a caspase-3 indicator based on FRET, inside living cells stably expressing SCAT3 during STS-induced apoptosis. At 0, 6 and 12h after STS treatment, the FRET efficiency of SCAT3 obtained by FES are consistent with that by two-photon excitation (TPE) fluorescence lifetime imaging microscopy (FLIM) in living cells stably expressing SCAT3. In this study, the FES was also used to analyze the caspase-3 activation in living cells during anti-cancer drug such as taxol, Artesunate (ART) or Dihydroartemisinin (DHA) treatment. Our results showed that ART or DHA induced apoptosis by a caspase-3-dependent manner, while caspase-3 was not involved in taxol-induced cell death. [Copyright &y& Elsevier]

Cancer severely threatens human health currently, promoting the rapid development of cancer treatment strategies. In addition to cancer therapy, assessment of cancer prognosis, which can evaluate the success with treatment and chances of recovery as well as assist to make subsequent therapeutic schedule, is also remarkably indispensable and important. Conventional technologies can't provide rapid and highly-sensitive assessment of cancer prognosis at cytological level. Herein, an effective nitrogen doped carbon dots with intrinsic nucleolus-targeting capability and high fluorescence quantum yield are synthesized, characterized and employed for fluorescence imaging of nucleolus, which is closely related to the biological alteration of cancer cell. The cancer prognosis thus can be accurately (limit of detection: 50 nM) and rapidly (5 min) assessed at subcellular organelle level from nucleolar characteristics, which are visualized and analyzed by the captured fluorescence images. Outstanding assessment performance endows the proposed technology with great potential for future clinical research. [Display omitted] • Nitrogen doped carbon dots are synthesized for fluorescence imaging of nucleolus related to the biological alteration of cancer cell. • The cancer prognosis can be assessed at subcellular organelle level, which is not achievable using conventional technologies. • The proposed assessment method for cancer prognosis shows faster and more sensitive features as compared with AgNOR method. [ABSTRACT FROM AUTHOR]

In article number 1806620, Chen Jiang and co‐workers, inspired by the ability of activated platelets to track tumor metastasis, develop a novel activated plateletstargeting micelle for efficient anticancer drug delivery to primary and metastatic tumors. After specifically binding to activated platelets in circulation, the micelles capture circulating tumor cells (CTCs) through the "platelet bridge" and eliminate CTCs to prevent metastasis. [ABSTRACT FROM AUTHOR]

The frequent relapse and metastasis characteristics of triple negative breast cancer (TNBC) make it a fraught issue with very poor prognosis in clinic. An effective treatment for TNBC should prevent and even eliminate metastasis as well as suppress primary lesion expansion. Recent progress reveals that platelets can be recruited and activated by tumor cells through intercellular adhesion molecules (ICAM), and help aggressive circulating tumor cells (CTCs) form metastasis. Therefore, activated platelets are considered with possession of tumor‐homing, CTC‐capturing, and metastasis‐targeting abilities. In this work, a P‐selectin (expressed on activated platelet surface) targeting peptide (PSN) is modified on a redox‐responsive paclitaxel‐loaded micelle (PSN‐PEG‐SS‐PTX4 micelle) to utilize activated platelets as a "bridge" for interaction with cancer cells. The PSN‐modified micelle can easily adhere to the surface of activated platelets and subsequently capture CTCs in blood circulation. Compared to Taxol and PEG‐SS‐PTX4 micelle, PSN‐PEG‐SS‐PTX4 micelle also exhibits enhanced primary TNBC/metastasis targeting and penetrating effect through binding with tumor infiltrating platelets and thus significantly improves treatment outcome. More importantly, PSN‐PEG‐SS‐PTX4 micelle potently suppressed lung metastasis of TNBC and reduced incidence of distant liver metastasis. The activated platelet‐targeting redox‐responsive micelle system provides a promising prospect for the omnidirectional treatment of metastatic cancer. A novel P‐selectin targeting micelle with controlled drug release is designed to utilize activated platelets as an endogenous device for efficient drug delivery to metastatic tumors. The micelle captures and eliminates circulating tumor cells via binding with activated platelets to prevent metastasis as well as penetrates and accumulates at primary tumors or metastasis via tumor‐infiltrating activated platelets. [ABSTRACT FROM AUTHOR]