[In vivo tumor imaging and therapy based on near-infrared cadmium-free quantum dots].

Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging in vivo and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging in vivo and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.

MRI-Based Interstitial Fluid Velocity Analysis for Drug Delivery Efficiency Evaluation in Tumor.

There are many flow behaviors in solid tumors, including intravascular, bloodstream, and interstitial convection. Studies have shown that tumor interstitial fluid (TIF) is an important part of tumor microenvironment regulation and affects drug delivery and metabolism between tumor cells. Magnetic resonance imaging (MRI) is suitable for detecting the flow rates of liquids in tissues. Clinical phase contrast PC-MRI technology has been designed to observe the blood flow in large vessels such as arteries and veins; however, it is not sensitive enough to deal with slow flow velocity. Our previously developed vertical plane echo PC-MRI technology, the Velocity Mapping sequence, improved the signal-to-noise ratio (SNR) for measuring slow interstitial fluid rate. In this study, this sequence was used to determine the TIF flow rate in MDA-MB-231 human breast tumor cells used in BALB/c nude male mice. Two different sizes of contrast agents were intravenously injected, and the relationship between their distribution and the TIF flow rate was studied for the first time. Combining the results of clinical scanning showed that small-molecule DTPA-Gd (diethylenetriaminepentaacetic acid-gadolinium) was distributed immediately around the tumor margin after the injection. This distribution was positively correlated to the high flow rate area of the TIF before administration. In contrast, nanoparticles NaGdF4-PEG (polyethylene glycol) entered the tumor and reached their peak at 3 h. Drug distribution was negatively correlated with the high-flow-rate region of the TIF. Investigation of the TIF velocity can help better understand the fluid behavior in tumors and its role in drug delivery.

Glutathione-sensitive mesoporous nanoparticles loaded with cinnamaldehyde for chemodynamic and immunological therapy of cancer.

Chemodynamic therapy as a novel type of chemotherapy can damage the DNA structures and induce cell apoptosis and immunogenic cell death (ICD) through generating reactive oxygen species (ROS) to aggravate oxidative stress. Nonetheless, as an intrinsic antioxidative response of tumor cells, the expression of glutathione (GSH) can be upregulated to maintain the cellular redox balance and protect the tumor cells from ROS-mediated damage. In this context, it is feasible to simultaneously boost ROS generation and GSH depletion in tumor cells; however, the precise delivery and release of GSH scavengers at specific subcellular sites is of great importance. Herein, we propose a GSH-responsive mesoporous organosilica nanoparticle (MON)-based nanomedicine MON-CA-TPP@HA through sequentially covalently attaching triphenylphosphine (TPP) and electrostatically coating hyaluronic acid (HA) onto the surface of cinnamaldehyde (CA)-loaded MONs, known as MON-CA-TPP@HA, which has been demonstrated to be an extremely effective therapeutic strategy for cancer treatment through inducing ICD and apoptosis of breast cancer cells. Systematic in vitro experimental results clearly revealed that the nanomedicine can actively target the tumor cells with the help of HA, subsequently enter the tumor cells, and precisely bind with the mitochondria through TPP residues. Upon cleavaging the disulfide bond in the MONs triggered by over-expressed GSH within tumors, the CA molecules can be released inducing the excessive ROS in situ surrounding the mitochondria to activate oxidative stress to induce apoptosis and ICD of breast cancer cells. The results of the in vivo experiments confirm that the MON-CA-TPP@HA nanomedicine can effectively promote dendritic cell (DC) maturation and CD 8+ T cell activation and regulate the ratio of M1/M2 macrophages, which improve tumor immunosuppressive microenvironment. It is thus believed that the current nanomedicine has paved a new way for future cancer therapy.

Building in biologically appropriate multifunctionality in aqueous copper indium selenide-based quantum dots.

Advanced nanoplatforms equipped with different functional moieties for theranostics hold appealing promise for reshaping precision medicine. The reliable construction of an individual nanomaterial with intrinsic near-infrared (NIR) photofunction and magnetic domains is much desired but largely unexplored in a direct aqueous synthesis system. Herein, we develop an aqueous phase synthetic strategy for Mn2+ doping of ZnS shell grown on Zn-Cu-In-Se core quantum dots (ZCISe@ZnS:Mn QDs), providing the optimal NIR fluorescence quantum efficiency of up to 18.9% and meanwhile efficiently introducing paramagnetic domains. The relaxometric properties of the water-soluble Mn-doped QDs make them desirable for both the longitudinal and transverse (T1 and T2) magnetic resonance (MR) contrast enhancement due to the shell lattice-doped Mn2+ ions with slow tumbling rates and favoured spin-proton dipolar interactions with surrounding water molecules. Surprisingly, the incorporation of Mn2+ ions into the shell is found to significantly enhance the production of reactive oxygen species (ROS) by combining both the chemodynamic and photodynamic processes upon NIR light irradiation, showing great potential for efficient photo-assisted ablation of cancer cells. Furthermore, a broad-spectrum excitation range beneficial for bright NIR fluorescence imaging of breast cancer has been proven and offers high flexibility in the choice of incident light sources. Multiparametric MR imaging of the brain has also been successfully demonstrated in vivo.

Oncogene-targeting nanoprobes for early imaging detection of tumor.

Malignant tumors have been one of the major reasons for deaths worldwide. Timely and accurate diagnosis as well as effective intervention of tumors play an essential role in the survival of patients. Genomic instability is the important foundation and feature of cancer, hence, in vivo oncogene imaging based on novel probes provides a valuable tool for the diagnosis of cancer at early-stage. However, the in vivo oncogene imaging is confronted with great challenge, due to the extremely low copies of oncogene in tumor cells. By combining with various novel activatable probes, the molecular imaging technologies provide a feasible approach to visualize oncogene in situ, and realize accurate treatment of tumor. This review aims to declare the design of nanoprobes responded to tumor associated DNA or RNA, and summarize their applications in detection and bioimaging for tumors. The significant challenges and prospective of oncogene-targeting nanoprobes towards tumors diagnosis are revealed as well.

Polytonic Drug Release via Multi-Hierarchical Microstructures Enabled by Nano-Metamaterials.

″Nano-metamaterials″, rationally designed novel class metamaterials with multilevel microarchitectures and both characteristic sizes and whole sizes at the nanoscale, are introduced into the area of drug delivery system (DDS), and the relationship between release profile and treatment efficacy at the single-cell level is revealed for the first time. Fe3+ -core-shell-corona nano-metamaterials (Fe3+ -CSCs) are synthesized using a dual-kinetic control strategy. The hierarchical structure of Fe3+ -CSCs, with a homogeneous interior core, an onion-like shell, and a hierarchically porous corona. A novel polytonic drug release profile occurred, which consists of three sequential stages: burst release, metronomic release, and sustained release. The Fe3+ -CSCs results in overwhelming accumulation of lipid reactive oxygen species (ROS), cytoplasm ROS, and mitochondrial ROS in tumor cells and induces unregulated cell death. This cell death modality causes cell membranes to form blebs, seriously corrupting cell membranes to significantly overcome the drug-resistance issues. It is first demonstrated that nano-metamaterials of well-defined microstructures can modulate drug release profile at the single cell level, which in turn alters the downstream biochemical reactions and subsequent cell death modalities. This concept has significant implications in the drug delivery area and can serve to assist in designing potential intelligent nanostructures for novel molecular-based diagnostics and therapeutics.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Nanoprobe Based on Biominerals in Protein Corona for Dual-Modality MR Imaging and Therapy of Tumors.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a "protein corona" that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe3O4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe3O4 nanoparticles were prepared by treating oleate-capped Fe3O4 nanoparticles with Lemieux-von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe3O4 nanoparticles, endowing the Fe3O4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe3+ with tannic acid (TA) to construct Fe3O4@BSA-TAFeIII nanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a "hybrid" corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe3+, inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe3+ can boost the T1-weighted MR imaging performance, and the Fe3O4 nanoparticles serve as T2-weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.

Molecular imaging of tumour-associated pathological biomarkers with smart nanoprobe: From "Seeing" to "Measuring".

Although the extraordinary progress has been made in molecular biology, the prevention of cancer remains arduous. Most solid tumours exhibit both spatial and temporal heterogeneity, which is difficult to be mimicked in vitro. Additionally, the complex biochemical and immune features of tumour microenvironment significantly affect the tumour development. Molecular imaging aims at the exploitation of tumour-associated molecules as specific targets of customized molecular probe, thereby generating image contrast of tumour markers, and offering opportunities to non-invasively evaluate the pathological characteristics of tumours in vivo. Particularly, there are no "standard markers" as control in clinical imaging diagnosis of individuals, so the tumour pathological characteristics-responsive nanoprobe-based quantitative molecular imaging, which is able to visualize and determine the accurate content values of heterogeneous distribution of pathological molecules in solid tumours, can provide criteria for cancer diagnosis. In this context, a variety of "smart" quantitative molecular imaging nanoprobes have been designed, in order to provide feasible approaches to quantitatively visualize the tumour-associated pathological molecules in vivo. This review summarizes the recent achievements in the designs of these nanoprobes, and highlights the state-of-the-art technologies in quantitative imaging of tumour-associated pathological molecules.

Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence.

Background: Chronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively. Objective: Our objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association. Method: We recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF). Results: More severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD. Conclusions: The bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.

Hawthorn fruit acid consumption attenuates hyperlipidemia-associated oxidative damage in rats.

Context: Hyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage. Objective: The present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism. Materials and methods: Sprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR. Results: This study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway. Conclusion: HFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.

Bright, Magnetic NIR-II Quantum Dot Probe for Sensitive Dual-Modality Imaging and Intensive Combination Therapy of Cancer.

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Two-Pronged Intracellular Co-Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy.

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid-coated iron oxide nanoparticle is delivered as nanovaccine (IONP-C/O@LP) that can co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enables IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen-specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo.

The influence of surface charge on the tumor-targeting behavior of Fe3O4 nanoparticles for MRI.

Nanomedicine-based tumor-targeted therapy has emerged as a promising strategy to overcome the lack of specificity of conventional chemotherapeutic agents. "Passive" targeting caused by the tumor EPR effect and "active" targeting endowed by the tumor-targeting moieties provide promising biomedical utilities and cancer therapy strategies for nanomedicine. However, as the nanoparticles are exposed to biological fluids, a large number of protein molecules will be adsorbed on their surface, known as protein corona, which may alter the targeting ability of the nanoparticles. The impact of different protein corona on the "passive" and "active" targeting behaviors is still ambiguous. Herein, three kinds of aqueous soluble Fe3O4 nanoparticles with different surface modifications were synthesized and applied to explore the correlation between their protein corona and passive/active tumor-targeting abilities. In the in vitro and in vivo studies, the protein corona exhibited completely different effects on the active and passive cancer-targeting capability of the particles. The particles presented active cancer-targeting ability if there was enough interaction time between the particles and cells. This was mainly due to the dynamic evolution of the protein corona, the proteins of which may be outcompeted by the cancer cell membrane and determine the targeting abilities. Unfortunately, the protein corona also inevitably accelerated RES/MPS uptake after the particles were injected into the body, which almost completely disabled the active targeting abilities of the particles. We believe that this in-depth understanding of protein corona will provide new ideas on the tumor-targeting mechanisms of nanoparticles and present a feasible approach to designing targeted drugs in the future.

Nanotechnology-enhanced immunotherapy for metastatic cancer.

A vast majority of cancer deaths occur as a result of metastasis. Unfortunately, effective treatments for metastases are currently lacking due to the difficulty of selectively targeting these small, delocalized tumors distributed across a variety of organs. However, nanotechnology holds tremendous promise for improving immunotherapeutic outcomes in patients with metastatic cancer. In contrast to conventional cancer immunotherapies, rationally designed nanomaterials can trigger specific tumoricidal effects, thereby improving immune cell access to major sites of metastasis such as bone, lungs, and lymph nodes, optimizing antigen presentation, and inducing a persistent immune response. This paper reviews the cutting-edge trends in nano-immunoengineering for metastatic cancers with an emphasis on different nano-immunotherapeutic strategies. Specifically, it discusses directly reversing the immunological status of the primary tumor, harnessing the potential of peripheral immune cells, preventing the formation of a pre-metastatic niche, and inhibiting the tumor recurrence through postoperative immunotherapy. Finally, we describe the challenges facing the integration of nanoscale immunomodulators and provide a forward-looking perspective on the innovative nanotechnology-based tools that may ultimately prove effective at eradicating metastatic diseases.

Endoluminal Motion Recognition of a Magnetically-Guided Capsule Endoscope Based on Capsule-Tissue Interaction Force.

A magnetically-guided capsule endoscope, embedding flexible force sensors, is designed to measure the capsule-tissue interaction force. The flexible force sensor is composed of eight force-sensitive elements surrounding the internal permanent magnet (IPM). The control of interaction force acting on the intestinal wall can reduce patient's discomfort and maintain the magnetic coupling between the external permanent magnet (EPM) and the IPM during capsule navigation. A flexible force sensor can achieve this control. In particular, by analyzing the signals of the force sensitive elements, we propose a method to recognize the status of the motion of the magnetic capsule, and provide corresponding formulas to evaluate whether the magnetic capsule follows the motion of the external driving magnet. Accuracy of the motion recognition in Ex Vivo tests reached 94% when the EPM was translated along the longitudinal axis. In addition, a method is proposed to realign the EPM and the IPM before the loss of their magnetic coupling. Its translational error, rotational error, and runtime are 7.04 ± 0.71 mm, 3.13 ± 0.47∘, and 11.4 ± 0.39 s, respectively. Finally, a control strategy is proposed to prevent the magnetic capsule endoscope from losing control during the magnetically-guided capsule colonoscopy.

A Cyclodextrin-Hosted Ir(III) Complex for Ratiometric Mapping of Tumor Hypoxia In Vivo.

Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen-sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7-modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host-guest structure. The oxygen-responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.

Effects of dexmedetomidine on immune function, renal function and inflammatory factors of patients undergoing percutaneous nephrolithotomy under general anesthesia.

The present study was designed to determine the effects of dexmedetomidine on immune function, renal function and inflammatory factors in patients undergoing percutaneous nephrolithotomy under general anesthesia. A total of 177 patients with kidney calculi who underwent percutaneous nephrolithotomy in The Second Affiliated Hospital of Fujian Medical University were enrolled, in which 91 patients were treated with dexmedetomidine during surgery (research group) and 86 patients were not sedated during surgery (control group). The vital signs, renal function, inflammatory factors and immune function during surgery between the two groups were compared. Patients in the research group showed improved vital signs, renal function, inflammatory factors and immune function compared with the control group (P<0.05), and also experienced a significantly shorter hospitalization time (P<0.001). Therefore, the present results suggested that with a relatively high safety profile, use of dexmedetomidine for sedation can effectively protect renal and immune functions, and reduce the inflammatory response of patients during percutaneous nephrolithotomy. Thus, dexmedetomidine may have be potentially applied in clinical practice.

Quantitative Mapping of Glutathione within Intracranial Tumors through Interlocked MRI Signals of a Responsive Nanoprobe.

Studies reveal that malignant tumors feature uneven distributions of some key biomarkers across the entire tumorous region. Nevertheless, only very limited progress has been made towards non-invasive and quantitative detection of tumor-specific biomarkers in vivo, especially with clinically compatible imaging modalities. Reported here is an Fe3 O4 nanoparticle-based glutathione (GSH) responsive magnetic resonance imaging (MRI) probe that can form particle aggregates within tumors in vivo to give rise to strong GSH concentration dependent interlocked relaxivities. A quantitative correlation between the interlocked MRI signals and local GSH concentration was established, and further applied for mapping the heterogeneous distribution of GSH within an intracranial tumor (2.4 mm × 1.6 mm) in vivo. This methodology will offer a practical route for quantitatively mapping tumor-specific biomarkers in vivo with unlimited detection depth, which largely challenges optical-imaging-based approaches.

Dexmedetomidine suppresses the progression of esophageal cancer via miR-143-3p/epidermal growth factor receptor pathway substrate 8 axis.

Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, transwell migration and invasion assays and Western blot assay. The expression of miR-143-3p was measured by quantitative real-time PCR in esophageal cancer tissues and cells. The binding sites between miR-143-3p and epidermal growth factor receptor pathway substrate 8 (EPS8) were predicted by Starbase online software, and the combination was verified by dual-luciferase reporter assay. The murine xenograft model was established using KYSE150 cells to verify the function of DEX in vivo. DEX inhibited the proliferation and metastasis while accelerated the apoptosis of esophageal cancer cells. The abundance of miR-143-3p was lower in esophageal cancer tissues and cells than that in paring normal tissues and normal esophageal mucosal cells Het-1A. MiR-143-3p could be induced by DEX treatment in esophageal cancer cells, and miR-143-3p also suppressed the development of esophageal cancer. EPS8 was a functional target of miR-143-3p, and it played an oncogenic role in esophageal cancer. DEX inhibited the growth of tumor via miR-143-3p/EPS8 in vivo. DEX suppressed the growth and metastasis while facilitated the apoptosis of esophageal cancer cells through upregulating the abundance of miR-143-3p and reducing the level of EPS8 in vivo and in vitro, providing promising target for the treatment of esophageal cancer.