Deep Learning-Assisted Intelligent Artificial Vision Platform Based on Dual-Luminescence Eu(III)-Functionalized HOF for the Diagnosis of Breast and Ovarian Cancer.

Developing an advanced analytical method to detect spermine (Spm) and N-acetylneuraminic acid (NANA), the biomarkers of breast and ovarian cancers, respectively, is critical for the early diagnosis of the two cancers, which is very meaningful for women's health. Here, a deep learning-assisted artificial vision platform based on a dual-emission ratiometric fluorescence sensor is first constructed to monitor Spm and NANA. The ratiometric fluorescence sensor (Eu@TCBP-HOF, 1) can selectively detect Spm with high sensitivity based on "Turn-on" mode. After adding Spm, the new ratiometric fluorescence sensor (1-Spm, named 2) shows high sensitivity for NANA with "Turn-off" mode. Moreover, the fluorescence sensors can achieve an obvious fluorescence color response to Spm and NANA. Even in real saliva and serum samples, 1 and 2 still show high sensitivity and color responsiveness with limit of detection (LODs) of 0.5 µM for Spm and 0.96 µM for NANA. In virtue of different fluorescence responses, the DenseNet algorithm of deep learning assists the fluorescence sensors, which can simulate the human visual systems to identify fluorescence images and distinguish the concentration of Spm and NANA within 1 s with over 99% recognition accuracy. The intelligent artificial vision platform developed in this work may provide a prospective analytical method for the early diagnosis of female malignant tumors.

Biomimetic nanoprobe-augmented triple therapy with photothermal, sonodynamic and checkpoint blockade inhibits tumor growth and metastasis.

BACKGROUND: Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression. RESULTS: We describe a synergistic triple protocol combining photothermal and sonodynamic therapy (PTT and SDT), together with immune checkpoint blockade for the inhibition of breast cancer growth and metastases in the 4T1 mouse model. PTT and SDT are synergistically augmented by a novel multimodal imaging nanoprobe integrated with cancer cell membrane-biomimetic nanoparticles (CHINPs) loaded with superparamagnetic iron oxide (SPIO) and hematoporphyrin monomethyl ether (HMME). CHINPs exhibit excellent homologous tumor targeting, and are sequentially triggered by ultrasound and near infrared (NIR) light under the guidance of magnetic resonance, photoacoustic and photothermal imaging, leading to complete in situ tumor eradication and systemic anti-tumor immune activation. Further combination of this approach with immune checkpoint blockade therapy is shown to suppress tumor metastasis. CONCLUSION: This work provides proof-of-principle for triple therapy using multimodal imaging-guided PTT/SDT based on biomimetic nanoprobes in combination with immunotherapy to eliminate tumors.

Synthesis and fluorescent properties of europium(III) complexes based on novel coumarin derivatives.

Four novel coumarin fluorescence small-molecules were successfully prepared and validated by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, and mass spectrometry (MS). Their corresponding europium(III) complexes were synthesized and characterized. The ligand can emit green fluorescence in solutions, and the best concentration was 40 µmol/L. The emission peak of ligand has a red-shift with the increase of concentration and solvent polarity. And the effect of various substituents in ligand was ordered using fluorescence intensity as standard: -NO2 > -Cl > -OCH3 > -OH. The order of fluorescence quantum yield is in line with the order of fluorescence intensity. The title europium complexes exhibit red fluorescence of europium ion (Eu3+ ) with good thermal stability. The effect of various substituents in ligand on the fluorescence intensity of title europium complexes was also consistent with the earlier results. This suggests that the prepared coumarins fluorescence small-molecules and their corresponding europium complexes have potential application prospects in the field of optical materials.

Novel intramolecular charge transfer effect-based ligands and aggregation-induced emission-active europium complexes: synthesis, characterization, and fluorescence properties.

Two novel coumarin derivatives and the corresponding europium complexes were prepared using a simple procedure. The pH response of the ligand and the aggregation-induced emission (AIE) properties of the target europium complex were studied. The ligand had an intramolecular charge transfer (ICT) effect and was linearly and sharply responsive under acidic conditions. The goal europium complexes exhibited excellent AIE performance when subjected to increasing concentrations of target europium complex or proportion of poor solvent. The effect of substituents on fluorescence strength or thermogravimetric and electrochemical properties was further investigated. The target complexes displayed the typical fluorescence of europium. The fluorescence amplitude of the target europium complexes was enhanced by the addition of electron-donating groups to ligands. Thermogravimetric research findings indicated that the target complexes possessed extreme thermal stability. Electrochemistry discovery findings indicated that the highest occupied molecular orbit energy level of EuL1 was greater than EuL2 , but the lowest unoccupied molecular orbit energy level was smaller than that of EuL2 . These complexes could be applied in medicinal chemistry, substance chemistry, and fluorescence labelling areas.

Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. CONCLUSION: This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.

A sustainable, eco-friendly Tb/Eu-modified HOFs for ultrasensitive detection and efficient adsorption of carcinogens in complex water environments.

Developing a multifunctional material that can detect and remove carcinogens in water environments, simultaneously monitor their toxic metabolites in living organisms is significant for environmental remediation and human health. However, most research only focused on detection or adsorption carcinogens due to the difficulty of integrating multiple functions into one material, let alone monitoring their toxic metabolites. Here, a multifunctional Tb/Eu@TATB-HOF (1) is first developed to monitor two carcinogens, malachite green (MG) and its metabolites leucomalachite green (LMG), and simultaneously remove MG from the contaminated water. 1, as the dual-emission fluorescence sensor, can achieve ultrasensitive and highly visualized sensing for MG and LMG with different response modes. Even in actual samples, 1 still exhibits satisfactory sensing performances. As the adsorbent, 1 displays good recyclability and high adsorption capacity for MG. The sensing and adsorption mechanisms are explored through experiments and theoretical calculations. This work not only provides a novel insight for environmental remediation and human health through detection and removal of carcinogens, simultaneously monitoring their toxic metabolites, but first reveals the enormous potential of HOFs as multifunctional materials simultaneously for fluorescence sensing and adsorption.

A luminescent Eu@SOF film fabricated by electrophoretic deposition as ultrasensitive platform for styrene gas quantitative monitoring through fluorescence sensing and ANNs model.

Styrene is a harmful gas widely existing in the air, which can damage human organs. Therefore, it is very crucial to develop a sensitive, portable and simple sensor for monitoring styrene. Herein, we design and fabricate a luminescent Eu@TMA-ME/FTO film (F) through EPD method. F emits bright red light of Eu(III) ions and shows superior fluorescence response to styrene gas as a sensor, which enable real-time and quantitative monitoring for styrene gas. More importantly, F exhibits a linear response to styrene gas in a wide concentration range of 10-7 to 10-2 M and a low DL with 0.20 ppm. The efficient PET process to styrene induced by ME and the competitive absorption between styrene and F are responsible for the sensing mechanism. Besides, the detection of styrene solution is also investigated in deionized water, tap water and river water. For the further application, an intelligent ANNs model has been constructed to process the fluorescence sensing results, which can convert fluorescence sensing images to the concentration of styrene gas. The data demonstrates that ANNs model can accurately monitor the concentration of styrene gas via deep ML without tedious data processing.

Portable, Intelligent Fluorescence Sensing Platform for Dense Convolutional Network-Capable Detection of Indophenol Sulfate and Methylmalonic Acid Using a Luminescent Eu@HOF Film.

Indophenol sulfate (IS) and methylmalonic acid (MMA) are biomarkers of chronic kidney disease (CKD) and diabetes polyneuropathy (DPN), respectively. Portable and accurate monitoring of IS and MMA is very important to ensuring human health. The dense convolutional network (DenseNet) with image recognition has great potential in fluorescence sensing, but developing a platform with high precision and portability to diagnose the disease still faces huge challenges. Herein, we developed a high-sensitivity platform with a fluorescence material, a smartphone, and the DenseNet to monitor IS and MMA. A red-emitting Eu@PFC-13 (1) is prepared, and 1 shows high selectivity and low detection limits (DLs) to detect IS and MMA. The sensing mechanism of 1 toward IS and MMA is investigated by experiments and theoretical calculation. For detecting IS and MMA in serum and urine, 1 is fabricated into an Eu@PFC-13/AG (2) film with DLs of 1.4 and 1.6 µM, respectively. In addition, a portable smartphone platform is designed to monitor IS and MMA with high precision. Moreover, the DenseNet is constructed by Python, which can output the concentration of analytes by identifying fluorescence images and judge whether any is in a dangerous range. This work not only proposes a novel method that integrates a fluorescence material, a smartphone, and deep learning to detect analytes but also opens a new way for the diagnosis of CKD and DPN.

Photonic Hyperthermia Synergizes with Immune-Activators to Augment Tumor-Localized Immunotherapy.

Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.

Biomimetic, pH-Responsive Nanoplatforms for Cancer Multimodal Imaging and Photothermal Immunotherapy.

Photothermal therapy (PTT), by converting light to thermal energy, has become a novel and noninvasive technique for tumor thermal ablation in clinical practice. However, as a result of phagocytosis of reticuloendothelial cells, current photothermal agents (PTAs) derived from exogenous materials suffer from incompetent tumor targeting and brief internal circulation time. The resulting poor accumulation of PTAs in the target area severely reduces the efficacy of PTT. In addition, the potential toxicity of PTAs, excessive laser exposure, and possibilities of tumor recurrence and metastasis following PTT are still intractable problems that severely influence patients' quality of life. Herein, a biomimetic pH-responsive nanoprobe was prepared via cancer cell membrane coating polydopamine (PDA)-CaCO3 nanoparticles (CPCaNPs) for photoacoustic (PA)/ultrasonic (US)/thermal imaging-guided PTT. When CPCaNPs targeted and infiltrated into the tumor's acidic microenvironment, the decomposed CO2 bubbles from homologous targeting CPCaNPs enhanced ultrasonic (US) signals obviously. At the same time, the PDA of CPCaNPs not only performed efficient PTT of primary tumors but also generated photoacoustic (PA) signals. In addition, an immune checkpoint pathway blockade was combined, which inhibited tumor recurrence and metastasis significantly and improved the immunosuppressive microenvironment after PTT to a large extent. Thus, these proposed biomimetic pH-responsive CPCaNPs provide a promising strategy for precise PTT immunotherapy under the intelligent guidance of PA/US/thermal imaging and show great potential for clinical translation.

Expression of Concern: Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery.

Expression of Concern for 'Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery' by Jianxin Liu et al., Biomater. Sci., 2018, 6, 2838-2849, https://doi.org/10.1039/C8BM00726H.

Engineering Fe/Mn-doped zinc oxide nanosonosensitizers for ultrasound-activated and multiple ferroptosis-augmented nanodynamic tumor suppression.

As an effective tumor-therapeutic modality, ultrasound-triggered sonodynamic therapy (SDT) has been extensively explored to induce cancer cell death by activating sonosensitizers to generate reactive oxygen species (ROS). However, the traditional inorganic semiconductor-based sonosensitizers still suffer from inefficient ROS production because of the low separation efficiency of electrons and holes (e-/h+) and their fast recombination. Herein, the iron (Fe) and manganese (Mn) co-doped zinc oxide nanosonosensitizers have been rationally designed and engineered for augmenting the SDT efficiency against tumor by inducing both multiple ferroptosis and apoptosis of tumor cells. The Fe/Mn component was co-doped into the nannostructure of ZnO nanosonosensitizers, which not only catalyzed the Fenton reaction in the hydrogen peroxide-overexpressed tumor microenvironment to produce ROS, but also depleted intracellular glutathione to suppress the consumption of ROS. The doping nanostructure in the engineered nanosonosensitizers substantially augmented the SDT efficacy of ZnO nanosonosensitizers by promoting the separation and hindering the recombination of e-/h+ under ultrasound activation. The multiple ferroptosis and apoptosis in the enhanced SDT effect of Fe/Mn co-doped ZnO nanosonosensitizers were solidly demonstrated both in vitro and in vivo on tumor-bearing mice in accompany with the detailed mechanism assessment by RNA sequenching. This work provides a distinct strategy to augment the nanomedicine-enabled SDT efficency by engineering the inorganic semiconductor-based nanosonosensitizers with transitional metal doping and inducing multiple cell-death pathways including ferroptosis.

Photosynthetic Oxygenation-Augmented Sonodynamic Nanotherapy of Hypoxic Tumors.

Reactive oxygen species (ROS) has been employed as a powerful therapeutic agent for eradicating tumor via oxidative stress. As an emerging ROS-involving noninvasive anticancer therapeutic modality, sonodynamic therapy (SDT) with high tissue penetration depth and benign remote spatiotemporal selectivity has been progressively utilized as the distinct alternative for ROS-based tumor treatment. However, the hypoxic tumor microenvironment substantially restricts the sonodynamic effect. In this work, an oxygen self-sufficient hybrid sonosensitizer on the basis of photosynthetic microorganisms cyanobacteria (Cyan) integrated with ultrasmall oxygen-deficient bimetallic oxide Mn1.4 WOx nanosonosensitizers, termed as M@C, is designed and engineered to overcome the critical issue of hypoxia-induced tumor resistance and strengthen the SDT effect. The sustained photosynthetic oxygen production by Cyan under light illumination can promote Mn1.4 WOx nanosonosensitizers to produce more ROS against cancer cells both in vitro and in vivo under ultrasound (US) irradiation. Especially, the sustained oxygen evolution for suppressing the gene expression of hypoxia-inducible factor 1alpha (HIF-1α) further boosts and augments the SDT efficiency. Thus, this work provides the paradigm that the rationally engineered biohybrid microorganism-based multifunctional sonosensitizers can serve as an effective bioplatform for augmenting the therapeutic efficiency of SDT, particularly for the treatment of hypoxic tumors.

Detection and Characterization of Sentinel Lymph Node by Ultrasound Molecular Imaging with B7-H3-Targeted Microbubbles in Orthotopic Breast Cancer Model in Mice.

PURPOSE: Accurate identification and assessment of sentinel lymph node (SLN) using noninvasive imaging methods can play a vital role in tumor staging, surgical planning, and prognostic evaluation. In this study, we assessed the efficacy of B7-H3-targeted molecular-ultrasound imaging for the early SLN detection, and characterization in a mouse model of orthotopic breast cancer. PROCEDURES: We established a mouse breast cancer model with lymph node metastasis by injecting MAD-MB 231 cells which were engineered to express firefly luciferase reporter gene into the fat pad of the right 4th mammary gland in female BALB/c nude mice. The sole lymph node (LN) close to the tumor was regarded as the SLN for imaging investigation, which included metastatic and non-metastatic SLNs. The LN in the right 4th mammary gland from normal mice was used as normal control (normal mice LN). The commercially available preclinical streptavidin-coated, perfluorocarbon-containing lipid-shelled microbubbles (VisualSonics, Toronto, Canada) were used to generate B7-H3-targeted microbubbles (MBB7-H3) and control microbubbles (MBControl). Then, ultrasound molecular imaging (USMI) was performed using a high-resolution transducer (MS250; center frequency, 21 MHz; Vevo 2100; VisualSonics, Toronto, Canada) after intravenous injection of microbubbles. RESULTS: The SLN was clearly detected and located under conventional (B-mode) and contrast-enhanced ultrasonography with microbubble injection. The metastatic SLNs showed a markedly higher signal from B7-H3-targeted microbubbles (MBB7-H3) compared to the non-metastatic SLNs and normal LNs. The metastatic SLN was further confirmed by ex vivo bioluminescence imaging and eventually verified by histological analysis. CONCLUSIONS: Our findings suggest the potential value of USMI using B7-H3 targeted microbubbles in breast cancer and establish an effective imaging method for the non-invasive detection and characterization of SLN.

Microorganism-enabled photosynthetic oxygeneration and ferroptosis induction reshape tumor microenvironment for augmented nanodynamic therapy.

Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) generation has been envisioned as a distinct modality for efficient cancer treatment. However, insufficient ROS generation and partial ROS consumption frequently limit the theraputic effect and outcome of NDT owing to the low oxygen (O2) tension and high glutathione (GSH) level in tumor microenvironment (TME). To circumvent these critical issues, we herein proposed and engineered the biodegradable GSH-depletion Mn(III)-riched manganese oxide nanospikes (MnOx NSs) with the photosynthetic bacterial cyanobacteria (Cyan) as a high-efficient and synergistic platform to reshape TME by simultaneously increasing oxygen content and decreasing GSH level. Specifically, under the trigger of acidity, MnOx NSs reacted with photosynthetic oxygen can generate toxic singlet oxygen (1O2). Moreover, MnOx NSs significantly reduced intracellular GSH, resulting in decreased GPX4 activity, which induced tumor cell non-apoptotic ferroptosis. Consequently, this combined strategy based on coadministration with Cyan and MnOx NSs demonstrated the superior antitumor efficacy via amplification of oxidative stress in 4T1 tumor-bearing mice for the synergetic oxygen-augmented nanodynamic/ferroptosis therapy. This work highlights a facile synergistic micro-/nano-system with the specific capability of reshaping TME to augment the sensitivity and therapeutic efficacy of NDT in solid hypoxic tumor therapy.

Ultrasound-Guided Microbubble-Mediated Locoregional Delivery of Multiple MicroRNAs Improves Chemotherapy in Hepatocellular Carcinoma.

Rationale: To assess treatment effects of 4 complementary miRNAs (miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21) encapsulated in a biodegradable PLGA-PEG nanoparticle, administered by an ultrasound-guided microbubble-mediated targeted delivery (UGMMTD) approach in mouse models of hepatocellular carcinoma (HCC). Methods:In vitro apoptotic index was measured in HepG2 and Hepa1-6 HCC cells treated with various combinations of the 4 miRNAs with doxorubicin. Three promising combinations were further tested in vivo by using UGMMTD. 63 HepG2 xenografts in mice were randomized into: group 1, miRNA-122/antimiRNA-10b/antimiRNA-21/US/doxorubicin; group 2, miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21/US/doxorubicin; group 3, miRNA-100/miRNA-122/antimiRNA-10b/US/doxorubicin; group 4, miRNA-122/anitmiRNA-10b/antimiRNA-21/doxorubicin; group 5, miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21/doxorubicin; group 6, miRNA-100/miRNA-122/antimiRNA-10b/doxorubicin; group 7, doxorubicin only treatment; and group 8, without any treatment. Tumor volumes were measured through 18 days. H&E staining, TUNEL assay, and qRT-PCR quantification for delivered miRNAs were performed. Results:In vivo results showed that UGMMTD of miRNAs with doxorubicin in groups 1-3 significantly (P<0.05) delayed tumor growth compared to control without any treatment, and doxorubicin only from day 7 to 18. On qRT-PCR, levels of delivered miRNAs were significantly (P<0.05) higher in groups 1-3 upon UGMMTD treatment compared to controls. TUNEL assay showed that upon UGMMTD, significantly higher levels of apoptotic cell populations were observed in groups 1-3 compared to controls. Toxicity was not observed in various organs of different groups. Conclusions: UGMMTD of miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21 combination improved therapeutic outcome of doxorubicin chemotherapy in mouse models of HCC by substantial inhibition of tumor growth and significant increase in apoptotic index.

Erratum: Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics: Erratum.

[This corrects the article DOI: 10.7150/thno.29569.].

PD-L1-targeted microbubbles loaded with docetaxel produce a synergistic effect for the treatment of lung cancer under ultrasound irradiation.

Immunotherapy is gradually becoming as important as traditional therapy in the treatment of cancer, but adverse drug reactions limit patient benefits from PD1/PD-L1 checkpoint inhibitor drugs in the treatment of non-small cell lung cancer (NSCLC). As a chemotherapeutic drug for NSCLC, docetaxel (DTX) can synergize with PD1/PD-L1 checkpoint inhibitors but increase haematoxicity and neurotoxicity. Herein, anti-PD-L1 monoclonal antibody (mAb)-conjugated and docetaxel-loaded multifunctional lipid-shelled microbubbles (PDMs), which were designed with biologically safe phospholipids to produce synergistic antitumour effects, reduced the incidence of side effects and promoted therapeutic effects under ultrasound (US) irradiation. The PDMs were prepared by the acoustic-vibration method and then conjugated with an anti-PD-L1 mAb. The material features of the microbubbles and their cytotoxic effects, cellular apoptosis and cell cycle inhibition were studied. A subcutaneous tumour model was established to test the drug concentration-dependent and antitumour effects of the PDMs combined with US irradiation, and an orthotopic lung tumour model simultaneously confirmed the antitumour effect of this synergistic treatment. The PDMs achieved higher cellular uptake than free DTX, especially when combined with US irradiation. The PDMs combined with US irradiation also induced an increased rate of cellular apoptosis and an elevated G2-M arrest rate in cancer cells, which was positively correlated with PD-L1 expression. An in vivo study showed that synergistic treatment had relatively strong effects on tumour growth inhibition, increased survival time and decreased adverse effect rates. Our study possibly provides a well-controlled design for immunotherapy and chemotherapy and has promising potential for clinical application in NSCLC treatment.

Thyroid cancer MR molecular imaging via SHP2-targeted nanoparticles.

BACKGROUND: Molecular imaging has generated a great demand to develop targeted contrast agents for MR imaging. MATERIALS AND METHODS: In this study, we synthesized Src homology 2-containing phosphotyrosine phosphatase 2 (SHP2)-targeted and polylactic-co-glycolic acid--based nanoparticles (NPs), which encapsulated perfluoropentane and being chelated with gadolinium (Gd3+) as an efficient molecular probe for targeting MR imaging on thyroid carcinoma. RESULTS: These NPs displayed practical properties and favorable biocompatibility in vitro. Furthermore, they showed abilities to specifically target thyroid cancer and enhance MRI as a contrast agent in both in vitro and in vivo experiments. CONCLUSION: This novel MR molecular imaging based on this SHP2-targeted contrast agent provides a useful and non-invasive method for the early detection of thyroid carcinoma.