Synthesis and in vitro experiments of carcinoma vascular endothelial targeting polymeric nano-micelles combining small particle size and supermagnetic sensitivity.

Objective: To construct carcinoma vascular endothelial-targeted polymeric nanomicelles with high magnetic resonance imaging (MRI) sensitivity and to evaluate their biological safety and in vitro tumor-targeting effect, and to monitor their feasibility using clinical MRI scanner. Method: Amphiphilic block copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) was synthesized via the ring-opening polymerization of ε-caprolactone (CL) initiated by poly(ethylene glycol) (PEG), in which cyclic pentapeptide Arg-Gly-Asp (cRGD) was conjugated with the terminal of hydrophilic PEG block. During the self-assembly of PEG-PCL micelles, superparamagnetic γ-Fe2O3 nanoparticles (11 nm) was loaded into the hydrophobic core. The cRGD-terminated γ-Fe2O3-loaded polymeric micelles targeting to carcinoma vascular endothelial cells, were characterized in particle size, morphology, loading efficiency and so on, especially high MRI sensitivity in vitro. Normal hepatic vascular endothelial cells (ED25) were incubated with the resulting micelles for assessing their safety. Human hepatic carcinoma vascular endothelial cells (T3A) were cultured with the resulting micelles to assess the micelle uptake using Prussian blue staining and the cell signal intensity using MRI. Results: All the polymeric micelles exhibited ultra-small particle sizes with approximately 50 nm, high relaxation rate, and low toxicity even at high iron concentrations. More blue-stained iron particles were present in the targeting group than the non-targeting and competitive inhibition groups. In vitro MRI showed T2WI and T2 relaxation times were significantly lower in the targeting group than in the other two groups. Conclusion: γ-Fe2O3-loaded PEG-PCL micelles not only possess ultra-small size and high superparamagnetic sensitivity, also can be actively targeted to carcinoma vascular endothelial cells by tumor-targeted cRGD. It appears to be a promising contrast agent for tumor-targeted imaging.

[A preliminary study of dual-source computed tomography dual energy imaging in the diagnosis of acute traumatic bone marrow lesions in spine].

OBJECTIVE: To explore the feasibility of virtual noncalcium technique from dual-source computed tomography (DSCT) for the diagnosis of vertebral bone marrow lesions. METHODS: A total of 13 patients with acute vertebral bone marrow lesions underwent both DSCT and MRI within 3 days. And the DSCT dual-energy CT data were postprocessed for generating virtual noncalcium images and color-coded maps. Two radiologists analyzed the lesions of bone marrow by magnetic resonance (MR) imaging and virtual noncalcium images on a three-level. MR imaging interpretation served as the reference standard. Consistency check was conducted by using kappa statistics. And then the sensitivity of DSCT dual energy imaging was examined in the diagnosis of acute traumatic bone marrow lesions in spine. RESULTS: Among them, 13 vertebral body with bone marrow lesions were detected by MRI. The T2WI fat-suppression irregular high signal and slightly high density shadow under the background in noncalcium images corresponded to corresponding high signal areas on MRI. Interreader agreement was substantial for qualitative grading of DE CT images (κ = 0.629). The sensitivity of DSCT dual energy virtual noncalcium images in the diagnosis of acute traumatic bone marrow lesions in spine were 92.3% and 84.6% for observers 1 and 2. CONCLUSION: Distinct traumatic bone marrow lesions of spine may be diagnosed with a high sensitivity on virtual noncalcium images reconstructed from DSCT and color-coded maps. And it is worth further explorations.

Self-assembled recombinant camel serum albumin nanoparticles-encapsulated hemin with peroxidase-like activity for colorimetric detection of hydrogen peroxide and glucose.

The construction of enzyme mimics using protein protection layers possesses advantages of high biocompatibility and superior catalytic activity, which is desirable for biomedical applications including diseases diagnosis. Here, from E. coli expression system, recombinant protein of camel serum albumin (rCSA) from Camelus bactrianus was successfully obtained to encapsulate hemin via the self-assemble method without additional toxic organic reagents. As compared with that of horseradish peroxidase, the produced rCSA-hemin nanoparticles exhibited enhanced enzyme-mimicking activity and stability under harsh experimental conditions. Additionally, the steady-state kinetic analysis of rCSA-hemin in the solution revealed its higher affinity to the substrates. Therefore, a colorimetric detection method of H2O2 and glucose was constructed with a linear range of 2.5-500 µM with an LOD of 2.39 and 2.42 µM, respectively, which was also applied for the determination of glucose in the serum samples with satisfying recovery ratio ranging from 101.1% to 112.1%. The constructed camel protein-derived nanozyme system of remarkable stability holds promising potentials for the versatile biomedical uses.

A green electrolysis of silver-decorated MoS2 nanocomposite with an enhanced antibacterial effect and low cytotoxicity.

To tackle the devastating microbial infections for the public health, a continuous search for effective and safe nanobiocides based on their prominent nanoscale effects has been extensively explored during past decades. In this study, a green electrolysis method was employed to synthesize silver-doped molybdenum sulfide (Ag@MoS2) composite materials. The obtained nanocomposites exhibited a sheet-like structure with a large specific surface area, which contributed to the efficient loading and refined distribution of silver nanoparticles. G- E. coli and G + S. aureus were used as model bacteria for the antibacterial test, which revealed enhanced antibacterial activity of produced nanocomposites with an identified destructive effect on preformed biofilms. It was found that within 72 hour incubation, 20 µg mL-1 Ag@MoS2 was sufficient to inhibit the growth of E. coli and S. aureus without visible colony formation, pointing to a desirable long-term antibacterial activity. Further a mechanistic antibiosis study of Ag@MoS2 indicated the involvement of a generation of reactive oxygen species. Notably, owing to the well-distributed silver nanoparticles on the nontoxic MoS2 nanosheet, the cytotoxicity evaluation results revealed that produced nanocomposites exhibited negligible toxicity to mammalian cells, and thereby held promising potential for biomedical applications.

Bactrian camel serum albumins-based nanocomposite as versatile biocargo for drug delivery, biocatalysis and detection of hydrogen peroxide.

In response to extreme environmental conditions, Bactrian camels with largest population in China have evolved with the unique and extraordinary stress-tolerant mechanism in the bodies, in which the most abundantly secreted serum albumins contribute to an important role in diverse physiological activities such as maintaining osmotic pressure and transporting endogenous/exogenous molecules. In this study, we have for the first time purified Chinese Bactrian camel serum albumins (CSA) aimed at exploring their biomedical application. The mass spectrometric as well as structural analysis of CSA have revealed the sequence consensus and alpha-helix abundant structures among its heterologous proteins. Using desolvation methods, CSA-based nanoparticles have been prepared to encapsulate two substrate molecules including Doxorubicin (Dox) and hemin, which confers the versatility of nanocomposite. As drug delivery matrix, the Dox-loaded CSA nanoparticles displayed sustained release behaviors of DOX with the decreased cytotoxicity detected by both CCK-8 assay and real-time cell analysis. The CSA-hemin nanoparticles exhibited superior catalytic activities in the oxidation of Orange II comparable with horse radish peroxidase following a ping-pong mechanism. Furthermore, the constructed CSA-hemin nanoparticles were applied for the spectroscopic detection of H2O2 resulting in a wide linear calibration curve ranging from 5 to 400 µM with a detection limit of 3.32 µM.

Nanobodies derived from Camelids represent versatile biomolecules for biomedical applications.

Nanobodies are antigen binding variable domains of heavy-chain antibodies without light-chains, and these biomolecules occur naturally in the serum of Camelidae species. Nanobodies have a compact structure and low molecular weight when compared with antibodies, and are the smallest active antigen-binding fragments. Because of their remarkable stability and manipulable characteristics, nanobodies have been incorporated into biomaterials and used as molecular recognition and tracing agents, drug delivery systems, molecular imaging tools and disease therapeutics. This review summarizes recent progress in this field focusing on nanobodies as versatile biomolecules for biomedical applications.

GSH-responsive curcumin/doxorubicin encapsulated Bactrian camel serum albumin nanocomposites with synergistic effect against lung cancer cells.

The aim of this study was to prepare camel serum albumin (CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin (CCM) and doxorubicin (Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian ( Camelus bactrianus) CSA. The constructed CSA nanoparticles (CSA-NPs) with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite (CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione (GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drug-delivery matrix to exert synergistic effects.

The prevalence of lacunar infarct decreases with aging in the elderly: a case-controlled analysis.

BACKGROUND AND PURPOSE: Lacunar infarct (LI) is well known as a heterogeneous primary disorder of cerebral small vessel. Compelling results have demonstrated that age is a risk factor to the prevalence of LI. However, the relationship between age and the prevalence of LI remains obscure. It is essential to note the relationship between age and the prevalence of LI through more clinical data. METHODS: A total of 3,500 patients were included in the case-controlled study. All data were collected from the Examination Center of Magnetic Resonance Imaging, Lu'an People's Hospital from January 2014 to December 2015. A primary discharge diagnosis of LI was done, and all subjects were evaluated as retrospective data. The relationship between the risk factors and the prevalence of diabetes and the relationship between age and the prevalence of diabetes was analyzed. A chi-square test was used to analyze the associations between different variables. A one-way analysis of variance was used to test the equality of three or more means at one time by using variances. Statistical significance was defined as a P-value of <0.05. RESULTS: The one-way analysis of variance demonstrated that the prevalence of LI increased with age before 60 years and decreased with age after 69 years. The same results were found in both the male and the female subjects. These results showed that the age-related risk factors (hypertension, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking) have no relationship with the prevalence of LI on the basis of age. There is a significant difference among the different age ranges (P=0.0006). Two-tailed P-value (unpaired t-test) showed the mean significant difference between 30-39 years and 40-49 years (P=0.009) and between 70-79 years and 80-100 years (P=0.0196). F-test (to compare variances) demonstrated that the variances of the different age ranges are significantly different between 30-39 years and 40-49 years (P=0.0002), between 40-49 years and 50-59 years (P=0.0424), and between 70-79 years and 80-100 years (P=0.0003). CONCLUSION: The age-related risk factors (hypertension, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking) have no relationship with the prevalence of LI on the basis of age. A decreasing prevalence of LI with aging occurs in the elderly, while the prevalence of LI increases with aging in the young and in adults. This investigation implicates that age is not a risk factor for LI in the elderly.