Straightforward and robust synthesis of monodisperse surface-functionalized gold nanoclusters

Gold nanoclusters are small (1–3 nm) nanoparticles with a high surface area that are useful for biomedical studies and drug delivery. The synthesis of small, surface-functionalized gold nanoclusters is greatly dependent on the reaction conditions. Here, we describe a straightforward, efficient and robust room temperature one-pot synthesis of 2 nm gold nanoclusters using thioglucose as a reducing and stabilizing agent, which was discovered by serendipity. The resultant monodisperse gold nanoclusters are more stable than those generated using some other common methods. The carboxylic acid contained in the stabilizing agent on the cluster surface serves as anchor for nanocluster functionalization. Alternatively, the addition of thiols serves to functionalize the nanoclusters. The resulting non-cytotoxic nanoclusters are taken up by cells and constitute a tuneable platform for biomedical applications including drug delivery

Stingless bee honey incorporated cellulose hydrogel/poly(lactic-co-glycolic acid) patch as an alternative treatment for aphthous stomatitis

Aphthous stomatitis is a disease that often reappears, causing irritation and pain. Common topical medications to treat aphthous stomatitis are fast-dissolving synthetic drugs, sometimes with limited therapeutic effectiveness. In this study, a patch, composed of a stingless bee honey incorporated cellulose hydrogel layer and a poly(lactic-co-glycolic acid) (PLGA) layer, was fabricated as an alternative treatment for aphthous stomatitis. The composition of the honey patches was verified by the presence of a distinct physical structure, considerable wettability records and lower degradation percentages on the layers containing higher PLGA concentrations. The honey patches were capable to retard Eschericia coli in the early hours (0.5-2 hours) and Staphylococcus aureus in the late hours (2-4 hours) of application, with tolerable cell viability and cell closure. The therapeutic values of the honey patches in retarding bacterial growth and inducing cell closure recommend the developed patches to be used in aphthous stomatitis treatment

Imaging early endothelial inflammation following stroke by core shell silica superparamagnetic glyconanoparticles that target selectin

Activation of the endothelium is a pivotal first step for leukocyte migration into the diseased brain. Consequently, imaging this activation process is highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to the endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance imaging revealed that the targeted nanoparticles accumulated in the brain vasculature following acute administration into a clinically relevant animal model of stroke, though increases in selectin expression were observed in both brain hemispheres. Nonfunctionalized naked particles also appear to be a plausible agent to target the ischemic vasculature. The importance of these findings is discussed regarding the potential for translation into the clinic

Synthesis of Multi-Functional Nano-Vectors for Target-Specific Drug Delivery

Magnetic nanoparticles have gained attention in cancer therapy due to their non-toxic properties and high bio-compatibility. In this report, we synthesize a dual-responsive magnetic nanoparticle (MNP) that is sensitive to subtle pH and temperature change as in the tumor microenvironment. Thus, the functional doxorubicin (DOX)-loaded MNP (DOX-PNIPAM-PMAA@Fe3O4) can perform specific DOX releases in the cancer cell. The particle was characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta-potential, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The microscopy data revealed the particle as having a spherical shape. The zeta-potential and size distribution analysis data demonstrated the difference for the stepwise modified MNPs. The FTIR spectrum showed characteristic absorption bands of NH2-SiO2@Fe3O4, CPDB@Fe3O4, PMAA@Fe3O4, and PNIPAM-PMAA@Fe3O4. Drug-loading capacity and releasing efficiency were evaluated under different conditions. Through an in vitro analysis, we confirmed that PNIPAM-PMAA@Fe3O4 has enhanced drug releasing efficiency under acidic and warmer conditions. Finally, cellular uptake and cell viability were estimated via different treatments in an MDA-MB-231 cell line. Through the above analysis, we concluded that the DOX-loaded particles can be internalized by cancer cells, and such a result is positive and prospective

Synthesis of Multi-Functional Nano-Vectors for Target-Specific Drug Delivery

Magnetic nanoparticles have gained attention in cancer therapy due to their non-toxic properties and high bio-compatibility. In this report, we synthesize a dual-responsive magnetic nanoparticle (MNP) that is sensitive to subtle pH and temperature change as in the tumor microenvironment. Thus, the functional doxorubicin (DOX)-loaded MNP (DOX-PNIPAM-PMAA@Fe3O4) can perform specific DOX releases in the cancer cell. The particle was characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta-potential, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The microscopy data revealed the particle as having a spherical shape. The zeta-potential and size distribution analysis data demonstrated the difference for the stepwise modified MNPs. The FTIR spectrum showed characteristic absorption bands of NH2-SiO2@Fe3O4, CPDB@Fe3O4, PMAA@Fe3O4, and PNIPAM-PMAA@Fe3O4. Drug-loading capacity and releasing efficiency were evaluated under different conditions. Through an in vitro analysis, we confirmed that PNIPAM-PMAA@Fe3O4 has enhanced drug releasing efficiency under acidic and warmer conditions. Finally, cellular uptake and cell viability were estimated via different treatments in an MDA-MB-231 cell line. Through the above analysis, we concluded that the DOX-loaded particles can be internalized by cancer cells, and such a result is positive and prospective

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV–vis absorption peak was detected in the range of 700–1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur–Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV–vis absorption peak was detected in the range of 700–1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur–Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231

Mannosyl electrochemical impedance cytosensor for label-free MDA-MB-231 cancer cell detection

A label-free and ultrasensitive electrochemical impedance cytosensor was developed to specifically detect the breast cancer cells MDA-MB-231 via the interaction between the mannosyl glassy carbon electrode (GCE) and the overexpressed mannose receptors on the target cell surface. The mannosyl GCE was prepared through electrografting of the amino-functionalized mannose derivatives on GCE surface in which a covalent bond was formed between carbon of the electrode and the amino group of the mannose derivative. The fluorescent microscopy indicated that the electrode is specific for MDA-MB-231 cells, with good biocompatibility for viable captured cells. The derivative with a shorter alkyl linker, mannose-C2NH2, showed a better sensitivity than that with a longer linker, mannose-C6NH2. GCE modified with amino-functionalized galactose derivative, galactose-C2NH2, shows no function to the detection of MDA-MB-231 cells. The specific interaction between the mannosyl GCE and Con A (a mannose-binding lectin) or MDA-MB-231 breast cancer cells with overexpressed mannose receptors was determined through the change of peak separation in the cyclic voltammogram or the change of charge transfer resistance in the electrochemical impedance spectra (Nyquist plot) in the electrolytes containing a reversible redox couple [Fe(CN)6]3-/[Fe(CN)6]4-. The charge transfer resistance in the Nyquist plots linearly depended on the concentration of MDA-MB-231 cells (1.0 × 10-1.0 × 105 cells mL-1, with 10 cells mL-1 being the lower detection limit). Introducing 0.1% polyethylene glycol-200 (PEG-200) was able to prevent the interference caused by 1.0 × 103 HEK-293T cells mL-1, a non-cancer cell line (control)

Automated solid-phase synthesis of oligosaccharides containing sialic acids

A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively

Inhibiting Human Calcitonin Fibril Formation with Its Most Relevant Aggregation-Resistant Analog

The most common obstacles to the development of therapeutic polypeptides are peptide stability and aggregation. Human calcitonin (hCT) is a 32-residue hormone polypeptide secreted from the C-cells of the thyroid gland and is responsible for calcium and phosphate regulation in the blood. hCT reduces calcium levels by inhibiting the activity of osteoclasts, which are bone cells that are mainly responsible for breaking down the bone tissue or decreasing the resorption of calcium from the kidneys. Thus, calcitonin injection has been used to treat osteoporosis and Paget’s disease of bone. hCT is an aggregation-prone peptide with a high tendency to form amyloid fibrils. As a result, salmon calcitonin (sCT), which is different from hCT at 16-residue positions and has a lower propensity to aggregate, has been chosen as a clinical substitute for hCT. However, significant side effects, including immune reactions, have been shown with the use of sCT injection. In this study, we found that two residues, Tyr-12 and Asn-17, play key roles in inducing the fibrillization of hCT. Double mutation of hCT at these two crucial sites could greatly enhance its resistance to aggregation and provide a peptide-based inhibitor to prevent amyloid formation by hCT. Double-mutated hCT retains its ability to interact with its receptor in vivo. These findings suggest that this variant of hCT would serve as a valuable therapeutic alternative to sCT