Label-Free In Vivo Monitoring of Lipid Droplets for Real-Time Assessment of Adipose Activator-Induced Tumor Suppression.

To enhance our comprehension of the fundamental mechanisms driving tumor metabolism and metastasis, it is essential to dynamically monitor intratumoral lipid droplet (LD) and collagen processes in vivo. Traditional LD analysis in tumors predominantly relies on observations of in vitro cells or tissue slices, which unfortunately hinder real-time insights into the dynamic behavior of LDs during in vivo tumor progression. In this study, we developed a dual-modality imaging technique that combines coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy for in vivo monitoring of tumor LDs and collagen alterations, assisted by a murine breast cancer 4T1 cell-based dorsal skinfold window. Specifically, we accomplished real-time observations and quantitative analysis of the LD size, density, and collagen alignment within living tumors through CARS/SHG imaging. Additionally, our findings demonstrate that real-time LD monitoring provides a valuable means of assessing the efficacy of anticancer drugs in vivo. We evaluated the impact of adipose activators on lipid metabolism, oxidative stress, and tumor suppression by monitoring changes in LD size and density. Overall, this study highlights the potential of dual-modality CARS/SHG microscopy as a sensitive and flexible tool for antitumor therapeutic strategies.

Combining near infrared fluorescence and laser speckle imaging with optical tissue clearing for in vivo transcranial monitoring of cerebral blood vessels damaged by photodynamic nanoformulation.

In vivo near infrared (NIR) fluorescence imaging and laser speckle contrast imaging (LSCI) are emerging optical bioimaging modalities, which can provide information on blood vessels morphology, volume and the blood flow velocity. Optical tissue clearing (OTC) technique addresses a light scattering problem in optical bioimaging, which is imperative for the transcranial brain imaging. Herein, we report an approach combining NIR fluorescence and LSC microscopy imaging with OTC. A liposomal nanoformulation comprising NIR fluorescent dye ICG and photosensitizer BPD was synthesized and injected intravenously into mouse with OTC treated skull. Transcranial excitation of BPD in nanoliposomes resulted in the localized, irradiation dose dependent photodynamic damage of the brain blood vessels, which was manifested both in NIR fluorescence and LSC transcranial imaging, revealing changes in the vessels morphology, volume and the blood flow rate. The developed approach allows for bimodal imaging guided, localized vascular PDT of cancer and other diseases.

Noninvasive Nonlinear Optical Computational Histology.

Cancer remains a global health challenge, demanding early detection and accurate diagnosis for improved patient outcomes. An intelligent paradigm is introduced that elevates label-free nonlinear optical imaging with contrastive patch-wise learning, yielding stain-free nonlinear optical computational histology (NOCH). NOCH enables swift, precise diagnostic analysis of fresh tissues, reducing patient anxiety and healthcare costs. Nonlinear modalities are evaluated, including stimulated Raman scattering and multiphoton imaging, for their ability to enhance tumor microenvironment sensitivity, pathological analysis, and cancer examination. Quantitative analysis confirmed that NOCH images accurately reproduce nuclear morphometric features across different cancer stages. Key diagnostic features, such as nuclear morphology, size, and nuclear-cytoplasmic contrast, are well preserved. NOCH models also demonstrate promising generalization when applied to other pathological tissues. The study unites label-free nonlinear optical imaging with histopathology using contrastive learning to establish stain-free computational histology. NOCH provides a rapid, non-invasive, and precise approach to surgical pathology, holding immense potential for revolutionizing cancer diagnosis and surgical interventions.

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co-cultivation of an equal amount of LLC and P-MSCs. When P-MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P-MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P-MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small-size metastases for LLC + P-MSCs(i.v.) and larger ones for LLC + P-MSCs. The increase in the rate of LLC cell dissemination after the injection of P-MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P-MSCs co-inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P-MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P-MSCs are shown to increase LLC aggressiveness related to cancer-associated angiogenesis and metastasis activation in the long term.

Specific detection of CA242 by antibody-modified chiral symmetric double "N" metasurface biosensor.

In this work, a biosensor based on Fano resonance metasurface is proposed for the specific detection of CA242 which is a typical marker of pancreatic cancer. The biosensor consists of a chiral symmetric plasma double "N" structure, which utilises coherent coupling of bright and dark modes to generate Fano resonance, achieving suppression of radiation loss, concentrating and storing energy more efficiently in the structure, and contributing to increased sensitivity to changes in ambient refractive index, resulting in a sensitivity of the sensor of up to 842.8 nm /RIU. After a series of antibody functionalization modifications, the metasurface has become an immune biosensor that can specifically detect the tumor marker CA242 of pancreatic cancer. The detection of mixed and single antigen solutions with different concentrations has verified the high sensitivity, high specificity, and high linear relationship of the biosensor to CA242, and the detection limit is as low as 0.0692 ng/mL. It is superior to other common methods and breaks the traditional disadvantages of lower detection accuracy and greater damage in tumour detection methods. The detection of the wavelength shift of localized surface plasmon resonance in plasma metasurface has been successfully applied to the highly sensitive detection of tumor markers. This study demonstrates the sensitivity and maneuverability of the chiral symmetric double "N" plasmonic metasurface biosensor, suggesting the potential application of metamaterials in biosensing based on environmental refractive index changes.

The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

FRET-Modulated Fluorescence Lifetime-Traceable Nanocarriers for Multidrug Release Monitoring and Synergistic Therapy.

In situ monitoring multidrug release in complex cellular microenvironments is significant, and currently, it is still a great challenge. In this work, a smart nanocarrier with the capability of codelivery of small molecules and gene materials as well as with Förster resonance energy transfer (FRET)-modulated fluorescence lifetime is fabricated by integrating gold nanoparticles (the acceptor) into dual-mesoporous silica loaded with multiple drugs (the donor). Once internalized into tumor cells, in weakly acidic environments, the conformation switch of the polymer grafted on nanocarriers causes its shedding from the mesopores, triggering the release of drugs. Simultaneously, based on the strong overlap between the emission spectrum of donors and the absorption spectrum of the acceptors, any slight fluctuation of the dissociation of the drugs from nanocarriers can result in a change in the FRET-modulated lifetime signal due to the extraordinarily sensitive FRET signal to the separation distance between donors and acceptors. All these implied the potential applications of this nanoplatform in various biomedical fields that require the codelivery and real-time monitoring of multidrug-based synergistic therapy.

Multifunctional carbon dots for glutathione detection and Golgi imaging.

Glutathione (GSH) is present in almost every cell in the body and plays various integral roles in many biological processes. The Golgi apparatus is a eukaryotic organelle for the biosynthesis, intracellular distribution, and secretion of various macromolecules; however, the mechanism of GSH in the Golgi apparatus has not been fully elucidated. Here, specific and sensitive sulfur-nitrogen co-doped carbon dots (SNCDs) with orange-red fluorescence was synthesized for the detection of GSH in the Golgi apparatus. The SNCDs have a Stokes shift of 147 nm and excellent fluorescence stability, and they exhibited excellent selectivity and high sensitivity to GSH. The linear response of the SNCDs to GSH was in the range of 10-460 µM (LOD = 0.25 µΜ). More importantly, we used SNCDs with excellent optical properties and low cytotoxicity as probes, and successfully realized golgi imaging in HeLa cells and GSH detection at the same time.

Deep learning-based high-speed, large-field, and high-resolution multiphoton imaging.

Multiphoton microscopy is a formidable tool for the pathological analysis of tumors. The physical limitations of imaging systems and the low efficiencies inherent in nonlinear processes have prevented the simultaneous achievement of high imaging speed and high resolution. We demonstrate a self-alignment dual-attention-guided residual-in-residual generative adversarial network trained with various multiphoton images. The network enhances image contrast and spatial resolution, suppresses noise, and scanning fringe artifacts, and eliminates the mutual exclusion between field of view, image quality, and imaging speed. The network may be integrated into commercial microscopes for large-scale, high-resolution, and low photobleaching studies of tumor environments.

Hemoglobin Nanocrystals for Drugs Free, Synergistic Theranostics of Colon Tumor.

The conventional approach in cancer nanomedicine involves advanced drug nanocarriers delivering preloaded therapeutics to targeted tumor sites to maximize drug efficiency. However, both cancer drugs and nanocarriers inevitably produce side effects and systemic toxicity. Herein, hemoglobin nanocrystals (HbC) as drug-free theranostic nanoformulations with the tumor microenvironment (TME) activated diagnostic and therapeutic abilities towards colon tumors are introduced. HbC can release Fe2+ oxidized to Fe3+ in the Fenton reaction with tumor endogenous H2 O2 , concurrently with the generation of cytotoxic hydroxyl radicals (•OH) that allow for chemodynamic therapy (CDT). Furthermore, in situ-produced Fe3+ reacts with colon tumor-abundant H2 S, resulting in the production of Fe1- x S, which provides magnetic resonance imaging (MRI) contrast and allows for NIR light-inducible photothermal therapy (PTT). In vitro and in vivo studies revealed that HbC produced CDT towards 4T1 tumors, and MRI-guided, synergistically enhanced combination of CDT and PTT against H2 S abundant colon tumors (CT26), with negligible toxicity towards normal tissues, enlightening HbC as highly efficient and biocompatible TME activated theranostic nanoplatform specific against colon cancer without any traditional drugs and drug carriers.

Lipid Membrane Alterations in Tumor Spheroids Revealed by Fluorescence Lifetime Microscopy Imaging.

Three-dimensional (3D) cultured tumor spheroid models, as one type of in vitro model, have been proven to have more physiological similarities to in vivo animal models than cells in 2D cultures. Tumor spheroids have been widely used in preclinical experiments of anticancer drug treatments, providing reliable data in pathogenetic research. Currently, different 3D cell culture conditions, even in the same cell line, generate heterogeneous spheroids in morphology and size, resulting in different growth rates or drug-killing responses. Therefore, the measurement and evaluation of the properties of tumor spheroids have become highly demanding tasks with huge challenges. For functional characterization of tumor spheroids, the microenvironment sensitivity and quantitative properties of the fluorescence lifetime microscopy imaging (FLIM) technique have great advantages for improving the reliability of cell physiological testing. In this paper, we have proposed a FLIM-based approach to observe the lipid components labeled with Nile red of cells in both 3D and 2D cultures. The imaging data and analysis provided basic information on the sizes, morphologies, and cell membrane fluorescence lifetime values of the tumor spheroids. FLIM data showed that the microenvironment of the cell membrane in the 3D model was largely altered compared to that in the 2D culture. Next, a series of parameters that may influence the lipid components of tumor cells and tumor spheroids were tested by FLIM, including pH, viscosity, and polarity. The results showed that pH and viscosity contributed little to the change in fluorescence lifetime values, while the change in cell membrane polarity was the main cause of the alterations in fluorescence lifetime data, suggesting that cell membrane polarity should be considered a marker in distinguishing tumor spheroids from cellular physiological status. In conclusion, this FLIM-based testing process has been proven to be a quantitative method for measuring the differences between the cells of the 3D model from the 2D cultured cells with satisfactory sensitivity and accuracy, providing a high potential standard assay in the quality evaluation and control of tumor spheroids for future anticancer drug development.

Comparing the Impact of NIR, Visible and UV Light on ROS Upregulation via Photoacceptors of Mitochondrial Complexes in Normal, Immune and Cancer Cells.

The effect of UV/visible/NIR light (380/450/530/650/808/1064 nm) on ROS generation, mitochondrial activity and viability is experimentally compared in human neuroblastoma cancer cells. The absorption of photons by mitochondrial photoacceptors in Complexes I, III and IV is in detail investigated by sequential blocking with selective pharmaceutical blockers. Complex I absorbs UV/blue light by heme P450, resulting in a very high rate (14 times) of ROS generation leading to cell death. Complex III absorbs green light, by cytochromes b, c1 and c, and possesses less ability for ROS production (seven times), so that only irradiation lower than 10 mW cm-2 causes an increase in cell viability. Complex IV is well-known as the primary photoacceptor for red/NIR light. Light of 650/808 nm at 10-100 mW cm-2 generates a physiological ROS level about 20% of a basal concentration, which enhance mitochondrial activity and cell survival, while 1064 nm light does not show any distinguished effects. Further, ROS generation induced by low-intensity red/NIR light is compared in neurons, immune and cancer cells. Red light seems to more rapidly stimulate ROS production, mitochondrial activity and cell survival than 808 nm. At the same time, different cell lines demonstrate slightly various rates of ROS generation, peculiar to their cellular physiology.

A D-Shaped Polymer Optical Fiber Surface Plasmon Resonance Biosensor for Breast Cancer Detection Applications.

Fiber-optic biosensors have garnered significant attention and witnessed rapid development in recent years owing to their remarkable attributes such as high sensitivity, immunity to electromagnetic interference, and real-time monitoring. They have emerged as a potential tool in the realm of biomarker detection for low-concentration and small molecules. In this paper, a portable and cost-effective optical fiber biosensor based on surface plasmon resonance for the early detection of breast cancer is demonstrated. By utilizing the aptamer human epidermal growth factor receptor 2 (HER2) as a specific biomarker for breast cancer, the presence of the HER2 protein can be detected through an antigen-antibody binding technique. The detection method was accomplished by modifying a layer of HER2 aptamer on the flat surface of a gold-coated D-shaped polymer optical fiber (core/cladding diameter 120/490 µm), of which the residual thickness after side-polishing was about 245 µm, the thickness of the coated gold layer was 50 nm, and the initial wavelength in pure water was around 1200 nm. For low-concentration detection of the HER2 protein, the device exhibited a wavelength shift of ~1.37 nm with a concentration of 1 µg/mL (e.g., 5.5 nM), which corresponded to a limit of detection of ~5.28 nM. Notably, the response time of the biosensor was measured to be as fast as 5 s. The proposed biosensor exhibits the potential for early detection of HER2 protein in initial cancer serum and offers a pathway to early prevention of breast cancer.

Multidimensional quantitative characterization of the tumor microenvironment by multicontrast nonlinear microscopy.

Characterization of the microenvironment features of tumors, such as its microstructures, biomolecular metabolism, and functional dynamics, may provide essential pathologic information about the tumor, tumor margin, and adjacent normal tissue for early and intraoperative diagnosis. However, it can be particularly challenging to obtain faithful and comprehensive pathological information simultaneously from unperturbed tissues due to the complexity of the microenvironment in organisms. Super-multiplex nonlinear optical imaging system emerged and matured as an attractive tool for acquisition and elucidation of the nonlinear properties correlated with tumor microenvironment. Here, we introduced a nonlinear effects-based multidimensional optical imaging platform and methodology to simultaneously and efficiently capture contrasting and complementary nonlinear optical signatures of freshly excised human skin tissues. The qualitative and quantitative analysis of autofluorescence (FAD), collagen fiber, and intracellular components (lipids and proteins) illustrated the differences about morphological changes and biomolecular metabolic processes of the epidermis and dermis in different skin carcinogenic types. Interpretation of multi-parameter stain-free histological findings complements conventional H&E-stained slides for investigating basal cell carcinoma and pigmented nevus, validates the platform's versatility and efficiency for classifying subtypes of skin carcinoma, and provides the potential to translate endogenous molecule into biomarker for assisting in rapid cancer screening and diagnosis.

Oxygen self-supplied upconversion nanoplatform loading cerium oxide for amplified photodynamic therapy of hypoxic tumors.

Photodynamic therapy (PDT) has been widely used in preclinical trials for treating various tumors. However, the hypoxic environment of tumors and the limited penetration depth of ultraviolet light severely weaken the PDT effect. To solve the above problems, a near-infrared (NIR) light-triggered oxygen (O2) self-supplied phototherapeutic platform (UCNPs/CeO2/Ce6/BSA) for amplified PDT performance against solid tumors by alleviating tumor hypoxia has been rationally developed. The platform has excellent stability and can continuously decompose H2O2 for sustained O2 supply to synergize 1O2 generation, thus inducing an enhanced mortality rate (59%) of ID8 cells in vitro under hypoxic + H2O2 conditions. The growth of solid tumors was effectively inhibited and the mouse survival rate was dramatically enhanced via a superior PDT therapeutic performance. This reported study facilitated the positive development of multifunctional diagnosis and treatment platforms under long-wavelength excitation for O2 self-supplied tumor treatments.

Staging of Skin Cancer Based on Hyperspectral Microscopic Imaging and Machine Learning.

Skin cancer, a common type of cancer, is generally divided into basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). The incidence of skin cancer has continued to increase worldwide in recent years. Early detection can greatly reduce its morbidity and mortality. Hyperspectral microscopic imaging (HMI) technology can be used as a powerful tool for skin cancer diagnosis by reflecting the changes in the physical structure and microenvironment of the sample through the differences in the HMI data cube. Based on spectral data, this work studied the staging identification of SCC and the influence of the selected region of interest (ROI) on the staging results. In the SCC staging identification process, the optimal result corresponded to the standard normal variate transformation (SNV) for spectra preprocessing, the partial least squares (PLS) for dimensionality reduction, the hold-out method for dataset partition and the random forest (RF) model for staging identification, with the highest staging accuracy of 0.952 ± 0.014, and a kappa value of 0.928 ± 0.022. By comparing the staging results based on spectral characteristics from the nuclear compartments and peripheral regions, the spectral data of the nuclear compartments were found to contribute more to the accurate staging of SCC.

Promising Colloidal Rhenium Disulfide Nanosheets: Preparation and Applications for In Vivo Breast Cancer Therapy.

Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.

Tumor-Microenvironment-Activated NIR-II Nanotheranostic Platform for Precise Diagnosis and Treatment of Colon Cancer.

Rational design of tumor-microenvironment (TME)-activated nanoformulation for precisely targeted cancer treatment has recently attracted an enormous attention. However, the all-in-one TME-activated theranostic nanosystems with a simple preparation and high biocompatibility are still rarely reported. Herein, catalase nanocrystals (CatCry) are first introduced as a tumor microenvironment activatable nanoplatform for selective theranostics of colon cancer. They are engaged as (i) a "nanoreactor" for silver nanoparticles (AgNP) synthesis, (ii) a nanovehicle for tumor delivery of anticancer drug doxorubicin (DOX), and (iii) an in situ O2 generator to relief tumor hypoxia. When CatCry-AgNP-DOX nanoformulation is within a tumor, the intratumoral H2S turns AgNP into Ag2S nanoparticles, inducing a photothermal effect and NIR-II emission under 808 nm laser irradiation and also triggering DOX release. Simultaneously, CatCry catalyzes intratumoral H2O2 into O2, relieving hypoxia and enhancing chemotherapy. In contrast, when delivered to healthy tissue without increased concentration of H2S, the developed nanoformulation remains in the "off" state and no theranostic action takes place. Studies with colon cancer cells in vitro and a murine colon cancer model in vivo demonstrated that CatCry-AgNP-DOX delivered a synergistic combination of PTT and enhanced chemotherapy, enabling complete eradication of tumor with minimal side effects. This work not only introduces nanoplatform for theranostics of H2S-rich tumors but also suggests a general strategy for protein-crystal-based nanomedicine.

Metallo-Dye-Based Supramolecular Nanoassembly for NIR-II Cancer Theranostics.

Retaining intrinsic photophysical performance and efficient therapeutic efficacy of cyanine dyes in the second near-infrared (NIR-II) biowindow are challenges in the biomedical field. Herein, we develop a metal ion-assisted NIR-II fluorophore assembly strategy to modulate molecular arrangement behavior, thus overcoming the drawbacks and retaining the photophysical performance of cyanine dyes in aqueous media for cancer phototheranostics. By screening a series of metal ion-assisted fluorophore assemblies, we remarkably found gadolinium-based metallo-dye-supramolecular nanoassembly (denoted as Gd@IR1064) with the intrinsic optical properties of NIR-II cyanine dye (IR1064). Most intriguingly, the as-prepared Gd@IR1064 not only exhibits deep-tissue-penetrating NIR-II photoacoustic, fluorescence, and magnetic resonance imaging ability but also possesses enhanced photothermal conversion performance-induced hyperthermia, achieving a significant tumor elimination effect. Our study provides a promising guide for modulating dye arrangement with unique photophysical performance for biomedical applications.

NIR-II J-Aggregated Pt(II)-Porphyrin-Based Phosphorescent Probe for Tumor-Hypoxia Imaging.

The luminescence of traditional phosphorescence-based hypoxia probes is limited to the visible and first near-infrared wavelength regions (<1000 nm), which has defects of higher light scattering and lower penetration depth in contrast with the second near-infrared wavelength window (NIR-II, 1000-1700 nm) for optical bioimaging. Herein, 5,15-bis(2,6-bis(dodecyloxy)phenyl)-porphyrin platinum(II) (PpyPt) with J-aggregation induced NIR-II phosphorescence is reported. J-aggregates of PpyPt are confirmed by the X-ray diffraction data in the crystalline state. Moreover, the emission and excitation spectra of PpyPt in the solid states reveal NIR-II luminescence feature of PpyPt in J-aggregates. More importantly, by preparation of water-soluble PpyPt nanoparticles (PpyPt NPs4.76 ) with J-aggregates, it has NIR-II phosphorescent lifetime of microseconds and good oxygen-sensitivity in water. Moreover, the good biological hypoxia-sensing potential of PpyPt NPs4.76 is demonstrated in cells and 4T1-tumor-bearing mice. This study provides an efficient strategy to design NIR-II phosphorescent probe for sensitive tumor-hypoxia detection through the construction of J-aggregates.