Differently sized NaGdF(4) nanocrystals with narrow particle size distributions were synthesized by a high temperature approach. Upon ligand exchange, the as-prepared hydrophobic NaGdF(4) nanocrystals were transferred into water by using asymmetric PEGs simultaneously bearing phosphate and maleimide groups. Further investigations demonstrated that the water-soluble NaGdF(4) nanocrystals, coated by PEG bearing two phosphate groups on the same side, exhibit not only excellent colloidal stability in water and PBS buffer, but also higher T1 relaxivity than Gd-DTPA (Magnevist). Through "click" reaction between the maleimide residue on particle surface and thiol group from the partly reduced anti-EGFR monoclonal antibody (mAb), NaGdF(4)-PEG-mAb nanoprobes were constructed, and their biocompatibility and binding specificity were evaluated through in vitro experiments. A series of in vivo experiments were then carried out for detecting intraperitoneal tumor xenografts in nude mice by using magnetic resonance (MR) imaging technique. The results revealed that the NaGdF(4)-PEG-mAb probes possessed satisfying tumor-specific targeting ability and strong MR contrast enhancement effects.
The continuously growing demand for clean, sustainable power systems for consumer electronics, electric vehicles, and national grid storage is driving the research interest for electrochemical energy storage systems with better safety, lower cost, and higher energy density beyond current Li-ion battery. [1] Among alternative competitors, lithium sulfur (Li-S) battery has been considered as outstanding representative considering its high theoretical capacity (S: 1675 mAh g −1 and Li: 3860 mAh g −1), sustainability of S, and lowest reduction potential of Li (−3.04 V vs SHE). [2] Despite intensive efforts over decades, the Li-S battery still suffers from several detrimental issues associated with both cathode and anode. For S cathode, the diffusion of intermediates lithium polysulfides (LiPS) and sluggish S redox conversion kinetic cause unsatisfactory specific capacity, inferior rate performance, and rapid capacity degradation. [3] For Li anode, the uncontrollable dendrite growth and infinite volume expansion result in safety risk and low Coulombic efficiency (CE). [4] Therefore, it is highly urgent to design the kinetically advanced Li-S battery system with well-designed configuration for both LiPSsuppressed cathode and dendrite-free anode. Hollow carbon sphere nanoreactors with good electrical conductivity, large surface area, and enhanced structural stability have been widely applied as the host for secondary batteries to improve their electrochemical performance. [5] For example, as S cathode, a hollow porphyrin organic framework was designed for long cycling stability Li-S battery resulting from the physical confinement of LiPS. [6] Besides, double-shelled hollow carbon sphere was explored as a free-standing S host for highenergy-density Li-S battery. [7] As for Li anode, encapsulation of Li into the hollow carbon sphere was designed for high stable Li metal anode. [8] However, the shuttle effect and Li dendrite has not substantially been resolved because the physical effect only addresses the surface issue and not the root. To overcome this, integrating bare carbon nanostructures with catalysts, such as The lithium sulfur (Li-S) battery is a preferential option for next-generation energy storage technologies, but the lithium polysulfide shuttling, sluggish redox kinetics, and uncontrollable lithium dendrite growth hamper its commercial viability. Herein, well-dispersed single atom Zn-decorated hollow carbon spheres (Zn 1-HNC) are developed as dual-functional nanoreactors for polysulfides-suppressed sulfur cathodes (Zn 1-HNC-S) and dendrite-free lithium anodes (Zn 1-HNC-Li) simultaneously for high-capacity, high-rate, and long-cycling Li-S batteries with fast redox kinetics. Benefiting from its excellent electronic conductivity, high surface area (370 m 2 g −1), highly-effective active sites and protective carbon shell, the resultant nanoreactor possesses strong physical confinement, chemical anchoring, and exceptional electrocatalysis for polysulfides. Meanwhile, the nanoreactor with excellent lithiophilic ab...
Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
The protein, thyroid hormone‐responsive SPOT 14 homolog (Thrsp), has been reported to be a lipogenic gene in cultured hepatocytes, implicating an important role of Thrsp in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Thrsp expression is known to be regulated by a variety of transcription factors, including thyroid hormone receptor, pregnane X receptor, and constitutive androstane receptor. Emerging in vitro evidence also points to a critical role of liver X receptor (LXR) in regulating Thrsp transcription in hepatocytes. In the present study, we showed that Thrsp was up‐regulated in livers of db/db mice and high‐fat‐diet–fed mice, two models of murine NAFLD. Hepatic overexpression of Thrsp increased triglyceride accumulation with enhanced lipogenesis in livers of C57Bl/6 mice, whereas hepatic Thrsp gene silencing attenuated the fatty liver phenotype in db/db mice. LXR activator TO901317 induced Thrsp expression in livers of wild‐type (WT) and LXR‐β gene‐deficient mice, but not in LXR‐α or LXR‐α/β double‐knockout mice. TO901317 treatment significantly enhanced hepatic sterol regulatory element‐binding protein 1c (SREBP‐1c) expression and activity in WT mice, but failed to induce Thrsp expression in SREBP‐1c gene‐deficient mice. Sequence analysis revealed four LXR response‐element–like elements and one sterol regulatory element (SRE)‐binding site within a −2,468 ∼+1‐base‐pair region of the Thrsp promoter. TO901317 treatment and LXR‐α overexpression failed to induce, whereas overexpression of SREBP‐1c significantly increased Thrsp promoter activity. Moreover, deletion of the SRE site completely abolished SREBP‐1c–induced Thrsp transcription. Conclusion: Thrsp is a lipogenic gene in the liver that is induced by the LXR agonist through an LXR‐α–mediated, SREBP‐1c–dependent mechanism. Therefore, Thrsp may represent a potential therapeutic target for the treatment of NAFLD. (Hepatology 2013;58:617–628)
High‐efficiency lithium–sulfur (Li–S) batteries depend on an advanced electrode structure that can attain high sulfur utilization at lean‐electrolyte conditions and minimum amount of lithium. Herein, a twinborn holey Nb4N5–Nb2O5 heterostructure is designed as a dual‐functional host for both redox–kinetics–accelerated sulfur cathode and dendrite‐inhibited lithium anode simultaneously for long‐cycling and lean‐electrolyte Li–S full batteries. Benefiting from the accelerative polysulfides anchoring–diffusion–converting efficiency of Nb4N5–Nb2O5, polysulfide‐shutting is significantly alleviated. Meanwhile, the lithiophilic nature of holey Nb4N5–Nb2O5 is applied as an ion‐redistributor for homogeneous Li‐ion deposition. Taking advantage of these merits, the Li–S full batteries present excellent electrochemical properties, including a minimum capacity decay rate of 0.025% per cycle, and a high areal capacity of 5.0 mAh cm−2 at sulfur loading of 6.9 mg cm−2, corresponding to negative to positive capacity ratio of 2.4:1 and electrolyte to sulfur ratio of 5.1 µL mg−1. Therefore, this work paves a new avenue for boosting high‐performances Li–S batteries toward practical applications.
In article number 2002271, Qihua Yang, Zhong‐Shuai Wu and co‐workers report a single atom zinc decorated hollow carbon sphere with excellent electronic conductivity, highly‐effective catalytic active sites and strong lithiophilic properties as a dual‐functional nanoreactor for dendrite free, kinetically accelerated polysulfides conversion lithium–sulfur batteries with high‐capacity, high‐rate and long‐cycling characteristics.
Overexpression of human epidermal growth factor receptor 2 (HER2) plays important roles in tumorigenesis and tumor progression in breast cancer. Nuclear imaging of HER2 expression in tumors might detect all HER2-positive tumors throughout the body and guide HER2-targeted therapies for patients. We therefore aimed to develop a HER2-targeted peptide probe for breast cancer imaging. A novel SPECT imaging probe, 99m Tc-HYNIC-H6F, was prepared and then evaluated in breast cancer animal models. Methods: The HER2-targeted peptide H6F (YLFFVFER) was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC). 99m Tc-HYNIC-H6F was prepared, and the in vivo characteristics of 99m Tc-HYNIC-H6F were investigated in MDA-MB-453 (HER2-positive) and MDA-MB-231 (HER2-negative) models using small-animal SPECT/CT. Moreover, to investigate the specificity of the H6F peptide toward HER2 and the potential applications in monitoring therapies involving trastuzumab, unlabeled H6F and trastuzumab were used as blocking agents in cell competition studies and SPECT imaging. Results: A standard tricine/trisodium triphenylphosphine-3,39,3$-trisulfonate labeling procedure demonstrated that the radiochemical purity was greater than 95%. 99m Tc-HYNIC-H6F displayed excellent HER2-binding specificity both in vitro and in vivo. SPECT/ CT imaging revealed that the MDA-MB-453 tumors were clearly visualized (percentage injected dose per gram, 3.58 6 0.01 at 30 min after injection), whereas the signals in HER2-negative MDA-MB-231 tumors were much lower (0.73 6 0.22 at 30 min after injection). Tumor uptake of MDA-MB-453 was blocked by the coinjection of excess H6F but not by excess trastuzumab. Conclusion: The 99m Tc-HYNIC-H6F peptide probe specifically accumulates in HER2-positive tumors and is therefore promising for the diagnosis of HER2-positive cancers. Because 99m Tc-HYNIC-H6F and trastuzumab target different regions of the HER2 receptor, this radiotracer also has great potential for monitoring the therapeutic efficacy of trastuzumab by rechecking the expression level of HER2 without blocking effect during therapy. Br east cancer is the most frequent cancer and the second leading cause of cancer death among women worldwide. The great progress in breast cancer screening and early diagnosis in recent decades has significantly increased life expectancy and patient quality of life (1,2). The best-studied tumor-associated antigen in breast cancer is human epidermal growth factor receptor 2 (HER2), which is positive in approximately 20%-30% of all breast cancers (3-5). Moreover, overexpression of HER2 is also characterized as a major negative prognostic factor that is associated with higher mortality in early-stage disease, increased incidence of metastasis, and reduced time to relapse (6-8). Trastuzumab (Herceptin; Genentech), the first approved HER2-targeted humanized monoclonal antibody, is the standard-of-care treatment for patients with HER2-positive breast cancer. In several trials, trastuzumab has proven effective in combination with...
We recently designed and synthesized a Glu-c(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin α(v)β(3) and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether (99m)Tc-labeled RGD-BBN peptide could be used for the noninvasive detection of lung carcinoma by using small-animal single-photon emission computed tomography (SPECT)/CT. RGD-BBN peptide was conjugated with 6-hydrazinonicotinyl (HYNIC) and then radiolabeled with (99m)Tc using tricine and TPPTS as the coligands (TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate). The biodistribution, planar gamma imaging, and small-animal SPECT/CT studies of (99m)Tc-HYNIC(tricine)(TPPTS)-RGD-BBN ((99m)Tc-RGD-BBN) were performed in C57/BL6 mice bearing Lewis lung carcinoma (LLC) or bearing both inflammation and LLC. HYNIC-RGD-BBN possessed a dual integrin α(v)β(3) and GRPR binding capacity. (99m)Tc-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. (99m)Tc-RGD-BBN was superior to (18)F-FDG for distinguishing lung carcinoma from inflammation. The uptake of (99m)Tc-RGD-BBN in LLC xenografts was 2.69 ± 0.66% ID/g at 1 h postinjection (p.i.) and was decreased to 1.99 ± 0.61% ID/g at 2 h p.i. The inflammation uptake of (99m)Tc-RGD-BBN was 1.20 ± 0.32% ID/g at 1 h and 0.56 ± 0.17% ID/g at 2 h p.i., respectively. High pancreas uptake (25.76 ± 5.49%ID/g and 19.56 ± 6.78% ID/g at 1 and 2 h p.i., respectively) was also found due to the high GRPR expression of this organ. Small-animal SPECT/CT using (99m)Tc-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with (99m)Tc-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.
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