Fluorescence-Recovered Wearable Hydrogel Patch for In Vitro Detection of Glucose Based on Rare-Earth Nanoparticles.

The physiological state of the human body can be indicated by analyzing the composition of sweat. In this research, a fluorescence-recovered wearable hydrogel patch has been designed and realized which can noninvasively monitor the glucose concentration in human sweat. Rare-earth nanoparticles (RENPs) of NaGdF4 doped with different elements (Yb, Er, and Ce) are synthesized and optimized for better luminescence in the near-infrared second (NIR-II) and visible region. In addition, RENPs are coated with CoOOH of which the absorbance has an extensive peak in the visible and NIR regions. The concentration of H2O2 in the environment can be detected by the fluorescence recovery degree of CoOOH-modified RENPs based on the fluorescence resonance energy transfer effect. For in vivo detection, the physiological state of oxidative stress at tumor sites can be visualized through its fluorescence in NIR-II with low background noise and high penetration depth. For the in vitro detection, CoOOH-modified RENP and glucose oxidase (GOx) were doped into a polyacrylamide hydrogel, and a patch that can emit green upconversion fluorescence under a 980 nm laser was prepared. Compared with the conventional electrochemical detection method, the fluorescence we presented has higher sensitivity and linear detection region to detect the glucose. This improved anti-interference sweat patch that can work in the dark environment was obtained, and the physiological state of the human body is conveniently monitored, which provides a new facile and convenient method to monitor the sweat status.

A mechanoluminescent material, ZnS:Mn,Li, with enhanced brightness for visualizing dental occlusion.

Mechanoluminescent materials are characterized by high luminescence intensity, high repeatability, no external voltage activation, and a good linear relationship between stress and mechanoluminescence intensity within a certain range. Therefore, mechanoluminescent materials have attracted increasing attention from researchers in the fields of stress sensing, encryption and anti-counterfeiting, structural health monitoring, energy-saving lighting, intelligent wearable devices, and other fields. In this study, ZnS:Mn powders with different Mn2+ ratios and different ion doping were synthesized by a high-temperature solid-phase reaction, and the synthesis of various materials was characterized. Then, the optimal mechanoluminescence effect of the ZnS:1%Mn,1%Li material was obtained. The photoluminescence intensity of ZnS:1%Mn,1%Li was 16.7 times higher than that of the sample without doping with Li+, and the mechanoluminescence intensity was 1.64 times higher. Finally, polyethylene terephthalate (PET) film was combined with ZnS:Mn,Li mechanoluminescent powders to prepare flexible three-layer composite film. Based on this, a feasible strategy for the detection of temporomandibular disorders was proposed. The composite film is easy to use, economical, and safe, and has good mechanoluminescent performance, which has potential application value in the field of occlusal force detection and visualization.

Novel Dual-Mode NIR-II/MRI Nanoprobe Targeting PD-L1 Accurately Evaluates the Efficacy of Immunotherapy for Triple-Negative Breast Cancer.

Background: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19-23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy. Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate. Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ1) of 9.77 mM-1 s-1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system. Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.

NIR-II imaging-guided photothermal cancer therapy combined with enhanced immunogenic death.

Photothermal therapy has a remarkable effect on the destruction of tumors. It kills tumor cells by photothermal ablation and induces immunogenic cell death by activating the immune response in tumor tissues. However, inhibition of the tumor immune microenvironment suppresses PTT-induced body-specific anti-tumor immunity. In this study, we designed the GdOF@PDA-HA-R837-hydrogel complex to achieve NIR-II imaging-guided photothermal ablation and enhanced immune response. Due to the doping of Yb and Er elements and the presence of a polydopamine coating, the synthesized nanoparticles enable NIR-II and photoacoustic imaging of tumor tissues, which will help in the integration of multimodal tumor imaging for diagnosis and treatment. Polydopamine is used as a photothermal agent and drug carrier because of its excellent photothermal ability and high drug loading capacity under 808 nm near infrared light. Hyaluronic acid can bind to specific receptors on the surface of cancer cells, allowing nanoparticles to aggregate around the tumor, thus enhancing the targeting ability of nanoparticles. In addition, imiquimod (R837) has been used as an immune response modulator to enhance the immunotherapeutic effect. The presence of a hydrogel enhanced the retention effect of nanoparticles in the tumor. We demonstrate that the combination of photothermal therapy with immune adjuvants effectively induces ICD, which in turn stimulates the activation of specific anti-tumor immunity and enhances the effect of photothermal therapy in vivo.

Dual-targeting lanthanide-ICG-MOF nanoplatform for cancer Theranostics: NIR II luminescence imaging guided sentinel lymph nodes surgical navigation.

Sentinel lymph node imaging is important for breast tumor staging and prediction of postoperative metastasis. However, clinical sentinel lymph node imaging has limitations such as low specificity, low contrast, and short retention time. The combination of bio-conjugates chemistry and luminescence technology may achieve the specific targeting effect. In this research, we designed a dual-targeting composite nanoprobe (∼50 nm) using a metal-organic framework (MOF) as carrier, loaded with lanthanide and ICG, and combined with hyaluronic acid and folic acid to detect metastatic lymph nodes. The coupled hyaluronic acid and folic acid can target to the tumor cells and dentritic cells with a dual-targeting effect. The FA-HA/ZIF-8@ICG nanoprobes can accumulate rapidly in sentinel lymph node with a stronger luminescence intensity (1.6 times) than that of normal popliteal lymph nodes in vivo, thus distinguish metastatic sentinel lymph node from normal effectively. Furthermore, due to the MOF carrier, the integrated lanthanide and near-infrared dye by transferring the absorbed excitation energy from ICG to Nd3+ can enhance the signal-to-background ratio of NIR II imaging and have long retention time in vivo imaging. Finally, the FA-HA/ICG@Ln@ZIF-8 nanoplatform increased the penetration depth and contrast of imaging, prolonged the retention time, and achieved the sentinel lymph nodes surgical resection. This study has important implications for lymph node imaging and surgical navigation.

Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer.

Breast-conserving surgery (BCS) is the standard of care for early breast cancer patients, while the high ratio of reoperation is still a challenge due to inaccurate margin assessments. In patients with locally advanced or advanced breast cancer, radiotherapy is an important treatment for local control or improvement of quality of life. However, enhancing sensitization to radiotherapy is an unmet medical need. To solve the above clinical predicaments, a glutathione (GSH) exhausting virus-like silicon dioxide nanoprobe with Gd coating and folic acid (FA) modification is designed. After loading ICG in the mesopores, the VGd@ICG-FA probe efficiently targets tumor cells with high resolution, due to its virus-like morphology and folate acid anchoring. Especially, the fabricated nanoprobe enables the identification of tiny cancers and navigates precise surgery under NIR-II fluorescence imaging. Moreover, after the nanoprobes enter into the cytoplasm of cancer cells, tetrasulfide linkages in the silica framework are broken under the triggering of high GSH concentrations. In turn, the broken framework exhausts GSH to disrupt intracellular reactive oxygen species (ROS) homeostasis, and Gd produces more ROS under radiotherapy, further activating ferroptosis, and resulting in the enhancement of radiotherapy in breast cancer. Therefore, our nanoprobe exhibits tremendous potential as a NIR-II fluorescence imaging agent with no systematic side effects for precise cancer surgery and nanotherapeutics for boosting radiation sensitivity in future clinical translation of breast cancer.

Nd-Mn Molecular Cluster with Searched Targets for Oral Cancer Imaging.

In this research, we designed a novel NIR II luminescence imaging probe with targeting effect to accurately track oral squamous cell carcinoma (OSCC) cells. Massive gene expression data were processed by weighted gene co-expression network analysis to establish a network of relationships between genes. After clustering, correlation of clinical information, and gene functional enrichment analysis, MMP1 was predicted to be a biomarker/therapeutic target for OSCC cells. To obtain rare-earth probes with better luminescence in the NIR II region, we adjusted the doping ratio of the rare-earth element (Nd, Gd, Er, and Yb) fraction of the Nd-Mn molecular cluster to optimize its luminescence properties. The results of in vitro targeting experiments showed that Nd-Mn-MMP1Ab can target Cal-27 cells, demonstrating at the cellular level that the MMP1 gene is a biomarker for oral cancer, which also proves that the cancer targets predicted by the bioinformatics approach are correct.

Thermally activated upconversion luminescence and ratiometric temperature sensing under 1064 nm/808 nm excitation.

In this research, a thermally activated upconversion luminescence (UCL) probe with ratiometric temperature sensing under 1064 nm and 808 nm excitation was designed. Especially, Nd3+, Tm3+and Ce3+were doped in rare earth nanoparticles (RENPs) as UCL modulators. By optimizing the elements and ratios, the excitation wavelength is successfully modulated to 1064 nm excitation with UCL intensity enhanced. Additionally, the prepared RENPs have a significant temperature response at 1064 nm excitation and can be used for thermochromic coatings. The intensity ratio of three-photon UCL (1064 nm excitation) to two-photon UCL (808 nm excitation) as an exponential function of temperature can be used as a ratiometric temperature detector. Therefore, this designed thermochromic coatings may enable new applications in optoelectronic device and industrial sensor.

Recent advances in lanthanide-doped up-conversion probes for theranostics.

Up-conversion (or anti-Stokes) luminescence refers to the phenomenon whereby materials emit high energy, short-wavelength light upon excitation at longer wavelengths. Lanthanide-doped up-conversion nanoparticles (Ln-UCNPs) are widely used in biomedicine due to their excellent physical and chemical properties such as high penetration depth, low damage threshold and light conversion ability. Here, the latest developments in the synthesis and application of Ln-UCNPs are reviewed. First, methods used to synthesize Ln-UCNPs are introduced, and four strategies for enhancing up-conversion luminescence are analyzed, followed by an overview of the applications in phototherapy, bioimaging and biosensing. Finally, the challenges and future prospects of Ln-UCNPs are summarized.

Electromagnetic induction for reinforced concrete bursting: principles, simulations, experiments, and applications.

Reinforced concrete (RC) structures are widely used in the field of architecture. With the rapid development of highway construction all over the world, some such buildings need to be demolished. However, various traditional dismantling methods are either time-consuming and labor-intensive, or cause pollution and present certain safety hazards. In this research, COMSOL simulation and experimental verification of various schemes of electromagnetic heating used for bursting RC was carried out. Also, the conducted bursting experiments using electromagnetic waves-including microwaves-were further processed to verify their infeasibility. Finally, we proposed a feasible electromagnetic heating device for bursting RC. Compared with the traditional bursting technology, the device has the advantages of high efficiency, environmental protection, safety, and convenience, and has high social and practical value.

Machine Learning Enhanced Optical Spectroscopy for Disease Detection.

Optical spectroscopy plays an important role in disease detection. Improving the sensitivity and specificity of spectral detection has great importance in the development of accurate diagnosis. The development of artificial intelligence technology provides a great opportunity to improve the detection accuracy through machine learning methods. In this Perspective, we focus on the combination of machine learning methods with the optical spectroscopy methods widely used for disease detection, including absorbance, fluorescence, scattering, FTIR, terahertz, etc. By comparing the spectral analysis with different machine learning methods, we illustrate that the support vector machine and convolutional neural network are most effective, which have potential to further improve the classification accuracy to distinguish disease subtypes if these machine learning methods are used. This Perspective broadens the scope of optical spectroscopy enhanced by machine learning and will be useful for the development of disease detection.

Rare earth nanoparticles for sprayed and intravenous NIR II imaging and photodynamic therapy of tongue cancer.

In this research, rare earth nanoparticles coupled with dihydroartemisinin (DHA) and a targeted antibody (RENP-DHA-Cap) for sprayed NIR II imaging and photodynamic therapy (PDT) of tongue cancer were designed. Genetic algorithms combined with combinatorial chemistry were proposed and successfully achieved in a single optimized luminescent phosphor with enhanced NIR II and high upconversion luminescence (UCL) under a NIR laser of wavelength 980 nm or/and 808 nm. In particular, T1 magnetic resonance imaging (MRI) signals can be adjusted with the Gd ion concentration. In combination with the targeted antibody of capmatinib (Cap), precise NIR II imaging for in situ tongue cancer by a simple spray method can be achieved. Most importantly, NIR II imaging and PDT treatment can be realized with RENP-DHA-capmatinib injected intravenously. This orthogonal theranostic mode with precise diagnosis under 808 nm and targeted effective treatment under 980 nm may promote tongue cancer theranostics.

Gold Nanostars Combined with the Searched Antibody for Targeted Oral Squamous Cell Carcinoma Therapy.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral and maxillofacial region. Due to the special physiological and anatomical position of the oral cavity, the disease often has a significant impact on the chewing, swallowing, language, and breathing functions of patients. In recent years, with the development of medical molecular biology, molecular targeted therapy has received increasing clinical attention and has gradually become a new method for the treatment of malignant tumors. In this research, gold nanostars with a high photothermal effect combined with the searched targeted antibody were used for OSCC therapy. We use the data set in the public database and construct a gene co-expression module by weighted gene co-expression network analysis (WGCNA). It was found that the turquoise module and the midnight blue module had the greatest connection to tumorigenesis. Cytoscape software was used to analyze the important modules, and the top 10 genes of each module were selected; the survival analysis of the top 10 genes was carried out by gene expression profiling interactive analysis (GEPIA), which indicated that these genes (SERPINH1, MMP11, ADAM12, FADS3, SLC36A2, C1QTNF7, SCRG1, and APOBEC2) have statistical significance as key genes that are related to the tumorigenesis of OSCC. Then, the anti-SERPINH1 antibody targeted to SERPINH1 was chosen as the inhibitor and combined with gold nanostars for photothermal assisted targeted therapy. Thus, the searched key genes can be regarded as biomarkers and therapeutic targets for further precise diagnosis.

Dual-molecular targeted NIR II probe with enhanced response for head and neck squamous cell carcinoma imaging.

In this research, a fluorescent probe of 7-(diethylamine) coumarin derivatives with multiple binding sites to detect biothiols in tumor cell with strong NIR II luminescencein vivowas synthesized. The biothiols include cysteine (Cys) and glutathione (GSH) in tumor cells, and the tumor-response luminescence was proved by the cell experiment. Importantly, the monolayer functional phospholipid (DSPE-PEG) coating and aggregation induced emission (AIE) dye of TPE modification made the probe have good stability and biocompatibility with little luminescence quenching in aqueous phase, which was proved byin vitroandin vivoexperiments. The final aqueous NIR II probe combined with bevacizumab (for VEGF recognition in the cancer cells) and Capmatinib (for Met protein recognition in the cancer cells) has stronger targeted imaging on head and neck squamous cell carcinoma (HNSCC) cancer with intravenous injection. This GSH/Cys detection in the tumor cell and strong dual-molecular NIR II bioimagingin vivomay provide new strategy to tumor detection.

Exosome-based rare earth nanoparticles for targeted in situ and metastatic tumor imaging with chemo-assisted immunotherapy.

In this research, a tumor exosome system DOX/2DG@E-RENPs with good biocompatibility, low immunogenicity, and a high targeting effect was proposed for theranostics with high chemo-/starvation/immunotherapy efficiency. DOX and 2-deoxy-D-glucose (DOX/2DG) together with rare earth nanoparticles (RENPs) can be simultaneously carried on the exosome by endocytosis of tumor cells and then exocytosis in vitro. This platform has a good monodispersity with an average size of 70 nm, and the system can emit upconversion luminescence and NIR II luminescence under a single NIR laser. In particular, this exosome can target homing cancer cells and kill the origin tumor cells. The strong targeting effect was proved by different cell lines with exosomes from different orthogonal cells (normal/cancer cells and human/mouse sources, respectively), and the in vivo NIR II imaging guided targeted cancer imaging and liver metastases can be realized by intravenous injection of E-RENPs. Furthermore, the good targeted therapeutic effect and in vivo NIR II imaging and metastases of this platform can be proved. The chemotherapy, starvation therapy, and immunotherapy (immune checkpoint inhibitors of an anti-PD-L1 antibody) could achieve effective synergistic therapy for lung adenocarcinoma, and the immunotherapy can be further proved by the clinical data. This will provide a new strategy for the precise targeting and treatment of tumors.

A Magnified Adaptive Feature Pyramid Network for automatic microaneurysms detection.

Diabetic retinopathy (DR), as an important complication of diabetes, is the primary cause of blindness in adults. Automatic DR detection poses a challenge which is crucial for early DR screening. Currently, the vast majority of DR is diagnosed through fundus images, where the microaneurysm (MA) has been widely used as the most distinguishable marker. Research works on automatic DR detection have traditionally utilized manually designed operators, while a few recent researchers have explored deep learning techniques for this topic. But due to issues such as the extremely small size of microaneurysms, low resolution of fundus pictures, and insufficient imaging depth, the DR detection problem is quite challenging and remains unsolved. To address these issues, this research proposes a new deep learning model (Magnified Adaptive Feature Pyramid Network, MAFP-Net) for DR detection, which conducts super-resolution on low quality fundus images and integrates an improved feature pyramid structure while utilizing a standard two-stage detection network as the backbone. Our proposed detection model needs no pre-segmented patches to train the CNN network. When tested on the E-ophtha-MA dataset, the sensitivity value of our method reached as high as 83.5% at false positives per image (FPI) of 8 and the F1 value achieved 0.676, exceeding all those of the state-of-the-art algorithms as well as the human performance of experienced physicians. Similar results were achieved on another public dataset of IDRiD.

MET-targeted NIR II luminescence diagnosis and up-conversion guided photodynamic therapy for triple-negative breast cancer based on a lanthanide nanoprobe.

In this research, degradable peptide-modified upconversion nanoparticles (ZUPEA) were designed for the NIR II imaging and upconversion luminescence (UCL) guided photodynamic therapy (PDT) of triple-negative breast cancer (TNBC). Ultra-small rare-earth nanoparticles (RENPs) and the polymer mPEG-PLGA are polymerized into nano-microspheres via a double emulsion synthesis method, and a photosensitizer molecule (ZnPc) is added during the polymerization process to generate ZUPEA. Under 980 nm excitation, this strategy enhanced the red emission at 650 nm, showing an energy transfer efficiency of 38.3%, and the designed RENPs have better NIR II imaging abilities with a core@shell structure. These ZUPEA nanoparticles have good photodynamic therapeutic effects in vitro, and they can be degraded into small nanoparticles with a size of less than 6 nm. The cMBP-peptide-modified luminescent probe can recognize MDA-MB-231 TNBC cells in vivo when intravenously injected due to the positive targeted imaging effects of the cMBP peptide toward MET and negative targeted imaging effects relating to enhanced permeability and retention (EPR ). This specially designed ZUPEA probe with integrated diagnosis and treatment functionality provides new ideas and prospects for the use of rare-earth nanoparticles in the clinical treatment of tumors.

NIR II Luminescence Imaging for Sentinel Lymph Node and Enhanced Chemo-/Photothermal Therapy for Breast Cancer.

In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS-DOX-Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd-DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd-DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments.

Targeted Luminescent Probes for Precise Upconversion/NIR II Luminescence Diagnosis of Lung Adenocarcinoma.

In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF4:Yb,Er,Eu@NaYF4:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the in vitro and in vivo animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and in vivo immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.

Met-Targeted Dual-Modal MRI/NIR II Imaging for Specific Recognition of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are one of the most common cancers with poor survival rates, which is attributed to the difficulty in the early detection of disease. However, conventional imaging methods lack accuracy and sensitivity in the early diagnosis of HNSCCs. Thus, there is an urgent need to develop an effective and sensitive approach for HNSCC imaging. As known, the cMet receptor is overexpressed in HNSCC tumor cells CAL27 and tumor tissues. Herein, we synthesize the dual-modal near-infrared II (NIR II) imaging of luminescence and T1 magnetic resonance imaging (MRI)-based nanoprobes with the cMet targeting binding peptide (NaGdF4-PEG-cMBP), which has strong upconversion/NIR II luminescence and higher R1 relaxivity compared with the commercially used gadolinium acid (5.871 vs 3.471 mM-1 s-1). Additionally, the luminescence imaging of Yb,Er,Ce-doped probes showed that the material can efficiently accumulate in HNSCC tumors with the cMet-targeted. It can be clearly visualized in both subcutaneous and orthotopic HNSCC tumor models by dual-modal T1-weighted MRI and NIR II luminescence imaging methods. The results demonstrate that our cMBP-conjugated nanoplatform may provide a novel and very efficient noninvasive diagnostic approach for HNSCC in the near future.