Shanmugavel Chinnathambi

Silicon Quantum Dots for Biological Applications

Semiconductor nanoparticles (or quantum dots, QDs) exhibit unique optical and electronic properties such as size-controlled fluorescence, high quantum yields, and stability against photobleaching. These properties allow QDs to be used as optical labels for multiplexed imaging and in drug delivery detection systems. Luminescent silicon QDs and surface-modified silicon QDs have also been developed as potential minimally toxic fluorescent probes for bioapplications. Silicon, a well-known power electronic semiconductor material, is considered an extremely biocompatible material, in particular with respect to blood. This review article summarizes existing knowledge related to and recent research progress made in the methods for synthesizing silicon QDs, as well as their optical properties and surface-modification processes. In addition, drug delivery systems and in vitro and in vivo imaging applications that use silicon QDs are also discussed.

Binding Mode of CpG Oligodeoxynucleotides to Nanoparticles Regulates Bifurcated Cytokine induction via Toll-like Receptor 9

The interaction of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) with Toll-like receptor 9 (TLR9) activates the immune system. Multimeric class A CpG ODNs induce interferon-α (IFN-α) and, to a lesser extent, interleukin-6. By contrast, monomeric class B CpG ODNs induce interleukin-6 but not IFN-α. This difference suggests that the multimerization of CpG ODN molecules is a key factor in IFN-α induction. We multimerized class B CpG ODN2006x3-PD molecules that consist entirely of a phosphodiester backbone onto quantum dot silicon nanoparticles with various binding modes. Herein, we present the binding mode–dependent bifurcation of cytokine induction and discuss its possible mechanism of CpG ODN and TLR9 interaction. Our discoveries also suggest that nanoparticles play roles in not only delivery of CpG ODNs but also control of CpG ODN activity.

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Background Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules. Methods For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO2 nanoparticles were prepared by coating SiO2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da). Results The capacity of the flake-shell SiO2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.

Fabrication of novel collagen-silica hybrid membranes with tailored biodegradation and strong cell contact guidance ability

The fabrication of novel collagen-silica hybrid membranes with tailored biodegradation and strong cell contact guidance ability is reported in the present study. Collagen-silica hybrids were first synthesized by reacting 3-glycidoxypropyltrimethoxysilane (GPTMS), which functioned as both the cross-linker and the silica source, with acid-soluble type I porcine collagen monomers. Subsequently, they were coated and dried on the surface of polydimethylsiloxane (PDMS) chips with either flat or microgroove surfaces to produce the corresponding collagen-silica hybrid membrane with a flat or microgroove surface. Scanning electron microscopy images showed that membranes formed on flat PDMS chips exhibited smooth and dense surfaces, while those formed on microgrooved PDMS chips exhibited typical microgroove surfaces with a 10 μm groove width, 8 μm ridge width, and 0.5 μm depth. Despite the difference in surface topography, both flat and microgrooved collagen-silica membranes exhibited stronger resistance against collagenase enzyme than the original collagen membrane due to the presence of silica, and the biodegradation rate of the samples was controllable through adjustment of the GPTMS content. Upon incubation with C2C12 skeletal myoblasts, both samples supported cell attachment, proliferation, and differentiation, suggesting good biocompatibility. However, a significant difference in cell morphology was observed. Cells on the flat membranes were randomly distributed, while those on the microgrooved samples were highly aligned and elongated, indicating that the microgrooved membranes exhibit much stronger cell contact guidance ability. The immunochemical assay showed that both flat and microgrooved samples supported the differentiation of C2C12 myoblasts to form multinucleated myotubes; however, the presence of the microgrooved surface topography significantly enhanced cell differentiation.

Generation of microgrooved silica nanotube membranes with sustained drug delivery and cell contact guidance ability by using a Teflon microfluidic chip

Abstract Silica nanotubes have been extensively applied in the biomedical field. However, very little attention has been paid to the fabrication and application of micropatterned silica nanotubes. In the present study, microgrooved silica nanotube membranes were fabricated in situ by microgrooving silica-coated collagen hybrid fibril hydrogels in a Teflon microfluidic chip followed by calcination for removal of collagen fibrils. Scanning electron microscopy images showed that the resulting silica nanotube membranes displayed a typical microgroove/ridge surface topography with ∼50 μm microgroove width and ∼120 μm ridge width. They supported adsorption of bone morphogenetic protein 2 (BMP-2) and exhibited a sustained release behavior for BMP-2. After culturing with osteoblast MC3T3-E1 cells, they induced an enhanced osteoblast differentiation due to the release of biologically active BMP-2 and a strong contact guidance ability to directly align and elongate osteoblasts due to the presence of microgrooved surface topography, indicating their potential application as a multi-functional cell-supporting matrix for tissue generation.

Synthesis of novel chitosan-silica/CpG oligodeoxynucleotide nanohybrids with enhanced delivery efficiency.

Chitosan-silica/CpG oligodeoxynucleotide (ODN) nanohybrids were synthesized to stimulate Toll-like receptor 9-mediated induction of interleukin-6 (IL-6). The chitosan-silica hybrid was first synthesized from a mixture of chitosan and 3-glycidoxypropyl trimethoxysilane under acidic conditions via a sol-gel process, and then used to condense CpG ODN2006x3-PD to yield chitosan-silica/CpG ODN nanohybrids. Scanning electron microscopy and atomic force microscopy showed that the chitosan-silica/CpG ODN nanohybrids had an elliptic shape with a diameter of 100-200 nm. After soaking in HAc-NaAc buffer solution (pH5.5), the nanohybrids exhibited sustained release of CpG ODN. When the nanohybrids were separately exposed to 293XL-hTLR9 cells and peripheral blood mononuclear cells, no significant toxicity was observed. An immunochemical assay for cellular uptake revealed that the nanohybrids were taken up by the cells and located in endolysosomes. An enzyme-linked immunosorbent assay for cytokines indicated that the nanohybrids effectively stimulated the induction of IL-6. Chitosan-silica/CpG ODN nanohybrids underwent cellular uptake and enhanced induction of IL-6 to a greater degree than conventional chitosan/CpG ODN nanocomplexes, indicating that they have an enhanced delivery efficiency.

Investigation of Optical Spectroscopic and Computational Binding Mode of Bovine Serum Albumin with 1, 4-Bis ((4-((4-Heptylpiperazin-1-yl) Methyl)-1H-1, 2, 3-Triazol-1-yl) Methyl) Benzene.

A newly synthesized 1, 4‐bis ((4‐((4‐heptylpiperazin‐1‐yl) methyl)‐1H‐1, 2, 3‐triazol‐1‐yl) methyl) benzene from the family of piperazine derivative has good anticancer activity, antibacterial and low toxic nature; its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of piperazine derivative to bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The molecular distance r between the donor (BSA) and acceptor (piperazine derivative) was estimated according to Forsters theory of nonradiative energy transfer. The physicochemical properties of piperazine derivative, which induced structural changes in BSA, have been studied by circular dichroism and those chemical environmental changes were probed using Raman spectroscopic analysis. Further, the binding dynamics was expounded by synchronous fluorescence spectroscopy and molecular modeling studies explored the hydrophobic interaction and hydrogen bonding results, which stabilize the interaction.

Underlying the Mechanism of 5-Fluorouracil and Human Serum Albumin Interaction: A Biophysical Study

5-Fluorouracil is clinically utilized as antitumor drug to treat numerous sorts of malignancy, which is made accessible to the objective tissues in conjugation with transport protein serum albumin furthermore which is low harmful when compared to the other drugs of this family and hence its binding characteristics are therefore of prime interest. The steady state and time resolved fluorescence studies, Fourier transform infrared spectroscopy and circular dichroism studies were employed to explain the mode and the mechanism of interaction of 5FU with HSA. 5-Fluorouracil binding is characterized with one high affinity binding site, with the binding constant of the order of 104. The molecular distance r (1.23 nm) between donor (HSA) and acceptor (5-FU) was estimated according to Forsters theory of non-radiative energy transfer. The feature of 5-Fluorouracil induced structural changes of human serum albumin has been studied in detail by Raman spectroscopy, circular dichroism and Fourier transform infrared spectroscopy analysis. The binding dynamics was expounded by synchronous fluorescence spectroscopy, fluorescence lifetime measurements and molecular modelling elicits that hydrophobic interactions and hydrogen bonding, stabilizes the 5-Fluorouracil interaction with HSA.

Synthesis and formulation of methotrexate (MTX) conjugated LaF3:Tb3+/chitosan nanoparticles for targeted drug delivery applications

Chitosan functionalized luminescent rare earth doped terbium nanoparticles (LaF3:Tb(3+)/chi NPs) as a drug carrier for methotrexate (MTX) was designed using a simple chemical precipitation method. The synthesized chitosan functionalized nanoparticles were found to be spherical in shape with an average diameter of 10-12nm. They are water soluble and biocompatible, in which the hydroxyl and amino functional groups on its surface are utilized for the bioconjugation of the anticancer drug, the methotrexate. The nature of MTX binding with LaF3:Tb(3+)/chi nanoparticles were examined using X-ray diffraction, zeta potential analyzer and transmission electron microscopy. The other interactions due to complex formation between MTX and LaF3:Tb(3+)/chi NPs were carried out by UV-Visible, steady and excited state fluorescence spectroscopy. The photo-physical characterization revealed that the adsorption and release of MTX from LaF3:Tb(3+)/chi NPs is faster than gold nanoparticles and also confirms that this may be due to weak interaction i.e. the Vander Waals force of attraction between the carboxyl and amino group of drug and nanoparticles. The maximum percentage yield and entrapment efficiency of 85.91±0.71 and 83.82± 0.14 were achieved at a stochiometric ratio of 4:5 of MTX and LaF3:Tb(3+)/chi nanoparticles respectively. In addition, antitumoral activity study reveals that MTX conjugated LaF3:Tb(3+)/chi nanoparticles show higher cytotoxic effect on MCF-7 breast cancer cell lines than that of free MTX.

Effect of Moderate UVC Irradiation on Bovine Serum Albumin and Complex with Antimetabolite 5-Fluorouracil: Fluorescence Spectroscopic and Molecular Modelling Studies

The interaction of antimetabolite 5-fluorouracil (5FU) with bovine serum albumin (BSA) under UVC (253.7 nm) irradiation was investigated in the present study using UV-Vis spectroscopy, steady state/time resolved fluorescence spectroscopic techniques. The stability of protein was found to be very strong when BSA gets bind to 5FU and moreover it is compared with the free BSA under UVC irradiation. From the fluorescence spectroscopic study, the stability of the complex was found to acquire 2-fold stronger than free protein. From the molecular modelling studies, we came to know the hydrogen bonds between BSA and antimetabolite 5FU are strong, up to 70.4 J/m2 under UVC irradiation.