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#29035819   2017/10/16 Save this To Up

Preparation of envelope-type lipid nanoparticles containing gold nanorods for photothermal cancer therapy.

The use of gold nanorods (AuNRs) that produce heat in response to near infrared (NIR) irradiation is an attractive approach to cancer photothermal therapy. AuNRs are usually prepared by using a highly toxic detergent: cetyltrimethylammonium bromide (CTAB). Thus, the removal of CTAB from the reaction mixture, and further stabilization of the surface of the AuNRs is required. In the present study, AuNRs were encapsulated in a multifunctional envelope-type nano device (AuNR-MEND) formed with an SS-cleavable and pH-activated lipid-like material. In the process of encapsulation, AuNRs were first stabilized with bovine serum albumin (AuNR-BSA), and then further encapsulated in the lipid envelope by the ethanol dilution method. The in vitro photothermal cytotoxicity of AuNR-MEND was further demonstrated on 4T1 breast cancer cells. After NIR radiation, the temperature of the medium was increased to approximately 60°C, and cell viability was drastically decreased to approximately 11%. However, this cytotoxic effect cannot simply be explained by medium heating. It therefore appears that intracellular delivery of the AuNRs is a key factor for achieving a high degree of cytotoxicity. Dose dependent cytotoxicity data revealed that a higher dose of AuNR-MEND resulted in the complete destruction of the cells when they were subjected to NIR irradiation, while the cell survival rate reached a plateau at 30% in the case of AuNR-BSA. Apoptosis was induced after treatment with the nanoparticles. AuNR-MEND showed superior cellular uptake activity over AuNR-BSA. Thus, delivering AuNR by means of functionalized lipid nanoparticles represents a promising approach to induce NIR-triggered apoptosis.

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#29035426   2017/10/16 Save this To Up

Synthesis of BSA-Coated BiOI@Bi2 S3 Semiconductor Heterojunction Nanoparticles and Their Applications for Radio/Photodynamic/Photothermal Synergistic Therapy of Tumor.

Developing an effective theranostic nanoplatform remains a great challenge for cancer diagnosis and treatment. Here, BiOI@Bi2 S3 @BSA (bovine serum albumin) semiconductor heterojunction nanoparticles (SHNPs) for triple-combination radio/photodynamic/photothermal cancer therapy and multimodal computed tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs possess strong X-ray attenuation capability since they contain high-Z elements, and thus they are anticipated to be a very competent candidate as radio-sensitizing materials for radiotherapy enhancement. On the other hand, as a semiconductor, the as-prepared SHNPs offer an extra approach for reactive oxygen species generation based on electron-hole pair under the irradiation of X-ray through the photodynamic therapy process. This X-ray excited photodynamic therapy obviously has better penetration depth in bio-tissue. What's more, the SHNPs also possess well photothermal conversion efficiency for photothermal therapy, because Bi2 S3 is a thin band semiconductor with strong near-infrared absorption that can cause local overheat. In vivo tumor ablation studies show that synergistic radio/photodynamic/photothermal therapy achieves more significant therapeutic effect than any single treatment. In addition, with the strong X-ray attenuation and high near-infrared absorption, the as-obtained SHNPs can also be applied as a multimodal contrast agent in CT/PA imaging.

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#29034405   2017/10/16 Save this To Up

Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but is less frequent in children. Antibodies against four antigens leading to MN have been described in children: phospholipase A2 receptor 1 (PLA2R1), thrombospondin type-1 domain-containing 7A (THSD7A), neutral endopeptidase (NEP), and cationic bovine serum albumin (BSA).

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#29030988   2017/10/14 Save this To Up

MiR-145-5p inhibits proliferation and inflammatory responses of RMC through regulating AKT/GSK pathway by targeting CXCL16.

The main pathological characteristics of chronic glomerulonephritis (CGN) are diffuse mesangial cells proliferation and inflammatory responses. Our previous studies have confirmed that miR-145-5p was abnormally elevated in CGN rats, but its mechanism remains unclear. Therefore, this study aimed to elucidate the mechanism of miR-145-5p in regulation of renal mesangial cells proliferation and inflammatory responses. In vivo study, the cationic bovine serum albumin(C-BSA)-induced CGN rat model was established, and the content of miR-145-5p in renal was examined by qRT-PCR, meanwhile, we also determined the renal function and inflammatory infiltrate. In vitro, the cell proliferation rate, cell cycle and inflammatory changes of rat mesangial cells (RMCs) were measured. Our results suggested that miR-145-5p extended the G0-G1 phase, shortened S phase, inhibited cell proliferation and suppressed inflammatory responses in RMCs. Moreover, miR-145-5p inhibited CXCL16 protein expression through binding the 3'-UTR of CXCL16, suppressed AKT/GSK signaling pathway, and decreased expression of inflammation related mRNAs, such as IL-1α, IL-2, IL-6, and TNF-α mRNAs. Further, locking CXCL16 alleviated inflammatory reactions and down-regulated AKT/GSK pathway in RMCs. Above all, we concluded that miR-145-5p inhibited proliferation and inflammatory responses of RMCs through regulation of AKT/GSK pathway by targeting CXCL16. This article is protected by copyright. All rights reserved.

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#29030194   2017/10/14 Save this To Up

Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistance in cancer cells.

Traditional spherical albumin nanoparticles remain the dominant shape of nano-carriers described in the literature at present, due to their simple desolvation method of synthesis. However, non-spherical shapes also show great promise as cancer drug delivery vectors. In this study, we report a novel synthetic strategy based on dimethyl sulfoxide (DMSO) addition during desolvation step, to produce doughnut-shaped bovine serum albumin nanoparticles (DBSA-NPs), while maintaining narrow size distributions and homogeneity. The characteristics such as size, polydispersity and doxorubicin (Dox) loading of prepared DBSA-NPs in comparison with spherical ones were determined. The biodegradation of DBSA-NPs loaded with doxorubicin (Dox-DBSA-NPs) in the presence of trypsin enzyme was spectrophotometrically monitored directly based on doxorubicin release profile. The release profile was analyzed with different kinetic models and it was best fitted with Higuchi kinetics model. The anticancer effect of Dox-DBSA-NPs against lymphoblastic leukemia (MOLT-4) and multidrug resistance uterine sarcoma (MES-SA/DX-5) cell lines were also investigated and the results were comparable with doxorubicin loaded spherical BSA nanoparticles (Dox-SBSA-NPs). These results showed the potential of Dox-DBSA-NPs as a novel and high potential nano-carrier for management of non-resistance and also multidrug resistant cancer cells.

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#29030191   2017/10/14 Save this To Up

Effect of pH and surfactant on the protein: A perspective from theory and experiments.

In the present study, we are aimed to explore the bovine serum albumin (BSA) and sodium dodecyl sulfate (SDS) interaction that can readily show the consequence of the change in concentration of protein with surfactants' various concentration and the different pH's, 4.0, 4.7, 7.0 of the medium through the many spectroscopic techniques. The BSA and SDS denaturation fully influenced by the pH. The results interpreted in terms of electrostatic and hydrophobic contributions to the stability of different phases formed in the system. Critical Micelle Concentration (CMC) of surfactant is influenced the protein folding and unfolding. The molecular docking supports the experiment data. This study demonstrates that the above and below the CMC of surfactant can significantly alter the binding interaction with the protein.

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#29029737   2017/10/14 Save this To Up

Surface enhanced infrared absorption spectroscopy based on gold nanostars and spherical nanoparticles.

Plasmonic anisotropic nanoparticles possess a number of hot spots on their surface due to the presence of sharp edges, tips or vertices, leading to a high electric field strength surrounding the nanostructures. In this paper, we explore different plasmonic nanostructures, including anisotropic gold nanostars (AuNSts) and spherical gold nanoparticles, in surface-enhanced infrared absorption spectroscopy (SEIRAS) in an attenuated total reflection (ATR) configuration. In our experiments, we observed up to 10-times enhancement of the infrared (IR) absorption of thioglycolic acid (TGA) and up to 2-times enhancement of signals for bovine serum albumin (BSA) protein on plasmonic nanostructure-based films deposited on a silicon (Si) internal reflection element (IRE) compared to bare Si IRE. The dependence of the observed enhancement on the amount of AuNSts present at the surface of the IRE has been demonstrated. Quantitative studies with both, TGA and BSA were performed, observing that the SEIRA signal can be correlated to the concentration of analyte molecules present within the evanescent field. The calibration curves in the presence of the AuNSts showed enhanced sensitivity as compared with the bare Si IRE. We finally compare efficiencies of anisotropic AuNSts and spherical citrate-capped and "bare" laser-synthesized gold nanoparticles as SEIRAS substrates for the detection of TGA and BSA. The signal obtained from AuNSts was at least 2 times higher for TGA molecules in comparison with spherical gold nanoparticles, which was explained by a more efficient generation of hot spots on anisotropic surface due to the presence of sharp edges, tips or vertices, leading to a high electric field strength surrounding the AuNSts.

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#29028503   2017/10/13 Save this To Up

Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin fibrillogenesis: Spectroscopic and microscopic study.

Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs7.4 and 3.5. The obtained results suggest that both the albumins forms amyloid-like aggregates in the presence of 1.0 to 15.0mM of TZ at pH3.5, but no amyloid fibril were seen at pH7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic and hydrophobic interaction because sulfate group of TZ may have interacted electrostatically with positively charged amino acids of the albumins at pH3.5 and increased protein-protein and protein-TZ interactions leading to amyloid fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms bigger size amyloids compared to HSA, may be due to high surface hydrophobicity of BSA.

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#29022633   2017/10/12 Save this To Up

In-site encapsulating gold "nanowires" into hemin-coupled protein scaffolds through biomimetic assembly towards the nanocomposites with strong catalysis, electrocatalysis, and fluorescence properties.

An efficient and green biomimetic assembly protocol was developed for the fabrication of multifunctional nanocomposites by mimicking the configuration of natural protein enzymes. Bovine serum albumin (BSA) as the protein model was first split to produce the disassembled BSA (dBSA) of linear polymer and then coupled with catalytic Hemin (Hem). The yielded dBSA-Hem scaffolds were utilized to in-site encapsulate gold nanoclusters (AuNCs) through biominerization, yielding the dBSA-Hem-AuNCs. It was discovered that the nanocomposites could display the well-defined composition and spheric morphology. In particular, they could exhibit unexpectedly strong catalysis, electrocatalysis, and fluorescence properties, in which the biominerized AuNCs would act as fluorescence sources and "nanowires" for promoting the electron-transfer of the catalytic nanocomposites. Colorimetric investigations show that the developed enzyme mimics could present peroxidase-like catalysis activities comparable to natural horseradish peroxidase. In addition, they could facilitate the direct electrocatalysis for H2O2 at concentrations as low as 0.40 μM. Moreover, strong red fluorescence of AuNCs in nanocomposites could be expected for the fluorimetric analysis of H2O2 with linear concentrations ranging from 50 nM to 100 μM. Such a biomimetic assembly route may open a new door toward the preparation of diverse nanocomposites with multifunctional catalysis and fluorescence, thus promising extensive applications of catalysis and detection in the chemical, environmental, and biomedical fields.

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#29019478   2017/10/11 Save this To Up

Engineering highly swellable dual-responsive protein-based injectable hydrogels: the effects of molecular structure and composition in vivo.

Stimuli-responsive hydrogels, known as smart hydrogels, are three-dimensional amphiphilic or hydrophilic polymer networks that are able to change their volume or phase, and other properties, including viscosity, structure, and dimension, in response to changes in pH, temperature, and magnetic or electric field. Highly swellable, dual-responsive bovine serum albumin (BSA)-based injectable hydrogels are prepared here by the chemical conjugation of pH- and temperature-responsive oligo(sulfamethazine acrylate-co-N-isopropylacrylamide) (oligo(SMA-co-NIPAM)) copolymers on the surface of BSA through carbodiimide-mediated chemistry. The pH- and temperature-responsive oligomer-bearing BSA conjugates show rapid sol-to-gel phase transition properties. Specifically, the free-flowing conjugates at high pH (pH 8.4, 23 °C) are transformed to a viscoelastic gel under physiological conditions (pH 7.4, 37 °C). The swelling ratio, gel strength, and pore size of the BSA hydrogel were tuned by altering the conjugation ratio of the oligo(SMA-co-NIPAM) copolymers of various lengths and compositions to BSA. Subcutaneously administered BSA conjugate sols into the dorsal region of Sprague-Dawley rats formed an in situ gel. When the oligo(NIPAM) content in the hydrogel was high, the degradation rate of BSA hydrogels was remarkably slow, and two weeks after in vivo administration, the hydrogels with high oligo(NIPAM) had swollen more than 4-fold. An in vivo biodegradation study demonstrated that no necrosis or hemorrhage was observed in the tissues with the hydrogels. The concurrent stimuli-responsivity under physiological conditions and high elasticity suggest that these smart hydrogels may open a new avenue for hydrogel applications.

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