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Purpose: Clinical applications of curcumin (Cur) have been greatly restricted due to its low solubility and poor systemic bioavailability. Three-arm amphiphilic copolymer tricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) nanoparticles (NPs) were designed to improve the solubility and bioavailability of Cur. The present study adopted a microchannel system to precisely control the preparation of self-assembly polymeric NPs via liquid flow-focusing and gas displacing method. Methods: The amphiphilic three-arm copolymer Tri-CL-mPEG was synthesized and self-assembled into nearly spherical NPs, yielding Cur encapsulated into NP cores (Cur-NPs). The obtained NPs were evaluated for physicochemical properties, morphology, toxicity, cellular uptake by A549 cells, release in vitro, biodistribution, and pharmacokinetics in vivo. Results: Rapidly fabricated and isodispersed Cur-NPs prepared by this method had an average diameter of 116±3 nm and a polydispersity index of 0.197±0.008. The drug loading capacity and entrapment efficiency of Cur-NPs were 5.58±0.23% and 91.42±0.39%, respectively. In vitro release experiments showed sustained release of Cur, with cumulative release values of 40.1% and 66.1% at pH 7.4 and pH 5.0, respectively, after 10 days post-incubation. The results of cellular uptake, biodistribution, and in vivo pharmacokinetics experiments demonstrated that Cur-NPs exhibited better biocompatibility and bioavailability, while additionally enabling greater cellular uptake and prolonged circulation with possible spleen, lung, and kidney targeting effects when compared to the properties of free Cur. Conclusion: These results indicate that Tri-CL-mPEG NPs are promising in clinical applications as a controllable delivery system for hydrophobic drugs.

Magnetic field has been considered to have positive effect on growth of bone. Because a magnetic nanoparticle can be regarded as one magnetic dipole, the macroscopic assemblies of magnetic nanoparticles may exhibit magnetic effect on local objects. This paper fabricated macroscopic film of γ-Fe2O3 nanoparticles by layer-by-layer (LBL) assembly on poly-D,L-lactic acid (PLA) scaffold, and studied the magnetic effect of the assembled γ-Fe2O3 nanoparticles film on primary bone marrow cells. The primary bone marrow cells were extracted from a mouse and cultured on the PLA substrate decorated by the film of γ-Fe2O3 nanoparticles after purification. Quantitative PCR (q-PCR) was used to show the cellular effect quantitatively. A just-found magnetosensing protein was employed to verify the magnetic effect of assembled film of nanoparticles on primary cells. It was exhibited that the decoration of nanoparticles enhanced the mechanical property of the interface. By acting as the adhesion sites, the LBL-assembled film of nanoparticles seemed beneficial to the cellular growth and differentiation. The expression of magnetosensing protein indicated that there was magnetic effect on the cells which resulted from the assembly of magnetic nanoparticles, implying its potential as a promising interface on scaffold which can integrate the physical effect with good biocompatibility to enhance the growth and differentiation of stem cells. The LBL-assembled film of magnetic nanoparticles may boost the development of novel scaffold which can introduce the physical stimulus into local tissue in vivo.

Synthesis of self-assembled monodisperse 3 nm FePd nanoparticles: Phase transition, magnetic study, and surface effect -cobalt nanoparticles with different shapes and sizes, e.g., rod-shaped Co (2ϫ25 nm) and ball-shaped Co ͑diameter 4 -9 nm͒, were synthesized by the rapid pyrolysis of octacarbonyldicobalt in o-dichlorobenzene solution in the presence of the surfactant, oleic acid. The size, size distribution, and the shape of the nanoparticles were influenced by changing the preparation conditions, such as the molar ratio of the surfactant ͑oleic acid͒ to reactant ͑cobalt carbonyl͒. The effects of the preparation conditions and annealing temperature on the shape and magnetic properties of cobalt nanoparticles have been investigated. It was found that as-synthesized rod-shaped cobalt nanoparticles (2ϫ25 nm) show paramagnetic properties, but as-synthesized ball-shaped cobalt nanoparticles exhibit superparamagnetic behavior. After postannealing at 773 K for 30 min, the rod-shaped Co nanoparticles formed hcp structure and show ferromagnetic properties.

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T 1 /T 2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T 1 and T 2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe 2 O 4 ) nanoparticle core. The results showed that the hydrophobic MnFe 2 O 4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM −1 s −1 , which was much higher than that of MnFe 2 O 4 nanoparticles (67.5 mM 1 s −1 ). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T 2 -weighted MR imaging. With the passage on, the Mn 2+ ions were released from MnFe 2 O 4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T 1 -weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe 2 O 4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T 1 - and T 2 -enhanced MR imaging of tumor angiogenesis.

BackgroundGoldMag nanoparticles (GMNPs) possess the properties of colloid gold and superparamagnetic iron oxide nanoparticles, which make them useful for delivery, separation and molecular imaging. However, because of the nanometer effect, GMNPs are highly toxic. Thus, the biosafety of GMNPs should be fully studied prior to their use in biomedicine. The main purpose of this study was to evaluate the nanotoxicity of GMNPs on human umbilical vein endothelial cells (HUVECs) and determine a suitable size, concentration and time for magnetic resonance imaging (MRI).ResultsTransmission electron microscopy showed that GMNPs had a typical shell/core structure, and the shell was confirmed to be gold using energy dispersive spectrometer analysis. The average sizes of the 30 and 50 nm GMNPs were 30.65 ± 3.15 and 49.23 ± 5.01 nm, respectively, and the shell thickness were 6.8 ± 0.65 and 8.5 ± 1.36 nm, respectively. Dynamic light scattering showed that the hydrodynamic diameter of the 30 and 50 nm GMNPs were 33.2 ± 2.68 and 53.12 ± 4.56 nm, respectively. The r2 relaxivity of the 50 nm GMNPs was 98.65 mM−1 s−1, whereas it was 80.18 mM−1 s−1 for the 30 nm GMNPs. The proliferation, cytoskeleton, migration, tube formation, apoptosis and ROS generation of labeled HUVECs depended on the size and concentration of GMNPs and the time of exposure. Because of the higher labeling rate, the 50 nm GMNPs exhibited a significant increase in nanotoxicity compared with the 30 nm GMNPs at the same concentration and time. At no more than 25 μg/mL and 12 hours, the 50 nm GMNPs exhibited no significant nanotoxicity in HUVECs, whereas no toxicity was observed at 50 μg/mL and 24 hours for the 30 nm GMNPs.ConclusionsThese results demonstrated that the nanotoxicity of GMNPs in HUVECs depended on size, concentration and time. Exposure to larger GMNPs with a higher concentration for a longer period of time resulted in a higher labeling rate and ROS level for HUVECs. Coupled with r2 relaxivity, it was suggested that the 50 nm GMNPs are more suitable for HUVEC labeling and MRI, and the suitable concentration and time were 25 μg/mL and 12 hours.

This study aimed to compare the diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis. 40 healthy Balb/c nude mice were selected. 0.1 ml of human lung cancer cell A549 bacterial suspension was injected by the left ventricle injection method to establish a lung cancer spinal metastasis model, and the abnormal signs of the nude mice were closely observed. When the body weight was reduced by 20%, micro PET/CT imaging and small coil MRI imaging were applied after intraperitoneal injection of thiopental anesthesia in nude mice. After the imaging was completed, the nude mouse was dissected and the spinal tumor was removed. The nature of spinal metastases was diagnosed by the pathology department. 5 nude mice died of abdominal infection, 2 nude mice had no spinal tumors, and the remaining 33 nude mice were successfully modeled. 33 nude mice were confirmed by pathology to have 64 metastatic vertebral lesions, among them, there were 7 cervical vertebrae, 24 thoracic vertebrae, 16 lumbar vertebrae, 6 sacral vertebrae and 11 caudal vertebrae. The sensitivity of MRI in the diagnosis of spinal metastases was 78.13%, and specificity was 56.25%. The sensitivity of PET/CT for the diagnosis of spinal metastases was 92.19%, and specificity was 78.95%. The specificity and positive predictive value of PET/CT for the diagnosis of spinal metastases were not significantly different from those of MRI (P> 0.05). The sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). PET/CT is superior to MRI in the diagnosis of spinal metastases, and its sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). It is worthy to be further promoted in clinical practice.