Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer.

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition.

Protein kinases belong to the phosphor-transferases superfamily of enzymes, which "activate" enzymes via phosphorylation. The kinome of an organism is the total set of genes in the genome, which encode for all the protein kinases. Certain mutations in the kinome have been linked to dysregulation of protein kinases, which in turn can lead to several diseases and disorders including cancer. In this review, we have briefly discussed the role of protein kinases in various biochemical processes by categorizing cancer associated phenotypes and giving their protein kinase examples. Various techniques have also been discussed, which are being used to analyze the structure of protein kinases, and associate their roles in the oncogenesis. We have also discussed protein kinase inhibitors and United States Federal Drug Administration (USFDA) approved drugs, which target protein kinases and can serve as a counter to protein kinase dysregulation and mitigate the effects of oncogenesis. Overall, this review briefs about the importance of protein kinases, their roles in oncogenesis on dysregulation and how their inhibition via various drugs can be used to mitigate their effects.

Influence of Green Synthesized Zinc Oxide Nanoparticles on Molecular Interaction and Comparative Binding of Azure Dye with Chymotrypsin: Novel Nano-Conjugate for Cancer Phototherapy.

Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a potent strategy for treating serious illnesses, including cancer-type feared diseases. The nanoparticles are a promising choice for cancer therapeutic and diagnostic applications because of their fascinating optoelectronic and physicochemical features. Among the metallic nanoparticles, Zinc oxide nanoparticles possess interesting physicochemical and anti-cancer characteristics, such as ROS generation, high retention, enhanced permeability etc., making them attractive candidates for the treatment and diagnosis of cancer. Zinc oxide nanoparticles showed anti-cancer property via excessive reactive oxygen species (ROS) production, and by the destruction of mitochondrial membrane. Here, we have synthesized organic/inorganic hybrid nanosystem composed of chymotrypsin protein (Chymo) with AzureC (AzC) conjugated with Zinc oxide nanoparticles (ZnONPs). The conjugation of AzureC with ZnONPs was confirmed by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) experiment. The interaction of Chymo with AzC alone and AzC-ZnONPs was investigated, and it was observed that the interaction was enhanced in the presence of ZnONPs, which was concluded by the results obtained from different spectroscopic techniques such as UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism in combination with molecular docking. UV-Visible spectroscopic studies and the corresponding binding parameters showed that the binding of AzC-ZnONPs complex with Chymo is much higher than that of AzC alone. Moreover, the fluorescence measurement showed enhancement in static quenching during titration of Chymo with AzC-ZnONPs as compared to dye alone. In addition to this, circular dichroism results show that the dye and dye-NPs conjugate do not cause much structural change in α-Chymo. The molecular docking and thermodynamic studies showed the predominance of hydrogen bonding, Van der Waal force, and hydrophobic forces during the interactions. After correlation of all the data, interaction of Chymo with AzC-ZnONPs complex showed strong interaction as compared to dye alone. The moderate binding with chymo without any alteration in the structure makes it desirable for the distribution and pharmacokinetics. In addition, the in vitro cytotoxicity of the AzC-ZnONPs was demonstrated on A-549 adenocarcinoma cell line. Our findings from physiochemical investigations suggested that the chymotrypsin coated AzC conjugated ZnONPs could be used as the novel nanoconjugates for various cancer phototherapies.

Green synthesis and physiochemical characterization of nickel oxide nanoparticles: Interaction studies with Calf thymus DNA.

One of the most promising applications of nanomaterials is that of nanobiosensors, using biomolecules such as nucleic acids as receptors. This study aimed to synthesize nickel oxide nanoparticles (NiO NPs) by an environmentally friendly green synthesis, using the extract of the herb Coriandrum sativum (coriander). The synthesized NPs were characterized using UV-Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photon spectroscopy, field emission scanning electron microscopy coupled with energy dispersive spectroscopy, dynamic light scattering, zeta potential and transmission electron microscopy. All results confirmed the synthesis of pure, spherical, positively charged NiO NPs of around 95 nm in diameter with prominent hydroxyl groups attached to the surface. Furthermore, interaction studies of synthesized NiO NPs with calf thymus DNA (CT DNA) were performed using UV-Visible spectroscopy, UV-thermal melting, circular dichroism, and fluorescence spectroscopy. CT DNA served as a substitute for nucleic acid biosensors. All experimental studies indicated that the NiO NPs bound electrostatically with CT DNA. These studies may facilitate exploring the potential of NiO NP-nucleic acid conjugated materials to be used as nanobiosensors for various applications, especially in pharmacological, epidemiological, and environmental diagnostic applications, and in detection.