Protein S antibody as an adjunct therapy for hemophilia B.

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

Evaluation of Ultra-Low-Dose Chest Computed Tomography Images in Detecting Lung Lesions Related to COVID-19: A Prospective Study.

Background: The present study aimed to evaluate the effectiveness of ultra-low-dose (ULD) chest computed tomography (CT) in comparison with the routine dose (RD) CT images in detecting lung lesions related to COVID-19. Methods: A prospective study was conducted during April-September 2020 at Shahid Faghihi Hospital affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In total, 273 volunteers with suspected COVID-19 participated in the study and successively underwent RD-CT and ULD-CT chest scans. Two expert radiologists qualitatively evaluated the images. Dose assessment was performed by determining volume CT dose index, dose length product, and size-specific dose estimate. Data analysis was performed using a ranking test and kappa coefficient (κ). P<0.05 was considered statistically significant. Results: Lung lesions could be detected with both RD-CT and ULD-CT images in patients with suspected or confirmed COVID-19 (κ=1.0, P=0.016). The estimated effective dose for the RD-CT protocol was 22-fold higher than in the ULD-CT protocol. In the case of the ULD-CT protocol, sensitivity, specificity, accuracy, and positive predictive value for the detection of consolidation were 60%, 83%, 80%, and 20%, respectively. Comparably, in the case of RD-CT, these percentages for the detection of ground-glass opacity (GGO) were 62%, 66%, 66%, and 18%, respectively. Assuming the result of real-time polymerase chain reaction as true-positive, analysis of the receiver-operating characteristic curve for GGO detected using the ULD-CT protocol showed a maximum area under the curve of 0.78. Conclusion: ULD-CT, with 94% dose reduction, can be an alternative to RD-CT to detect lung lesions for COVID-19 diagnosis and follow-up.An earlier preliminary report of a similar work with a lower sample size was submitted to the arXive as a preprint. The preprint is cited as: https://arxiv.org/abs/2005.03347.

Non-Invasive characterisation of renal stones using dual energy CT: A method to differentiate calcium stones.

BACKGROUND: Non-invasive DECT based characterization of renal stones using their effective atomic number (Zeff) and the electron density (ρe) in patients. AIM: This paper aims to develop a method for in-vivo characterization of renal stone. Differentiation of renal stones in-vivo especially sub types of calcium stones have very important advantage for better judgement of treatment modality. MATERIALS AND METHODS: 50 extracted renal stones were scanned ex-vivo using dual energy CT scanner. A method was developed to characterize these renal stones using effective atomic number and electron density obtained from dual energy CT data. The method and formulation developed in ex-vivo experiments was applied in in-vivo study of 50 randomly selected patients of renal stones who underwent dual energy CT scan. RESULTS: The developed method was able to characterize Calcium Oxalate Monohydrate (COM) and the combination of COM and Calcium Oxalate Dihydrate (COD) stones non-invasively in patients with a sensitivity of 81% and 83%respectively. The method was also capable of differentiating Uric, Cystine and mixed stones with the sensitivity of 100, 100 and 85.71% respectively. CONCLUSION: The developed dual energy CT based method was capable of differentiating sub types of calcium stones which is not differentiable on single energy or dual energy CT images.

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods.

Protein-ligand interaction studies are useful to determine the molecular mechanism of the binding phenomenon, leading to the establishment of the structure-function relationship. Here, we report the binding of well-known antibiotic sulfonamide drugs (sulfamethazine, SMZ; and sulfadiazine, SDZ) with heme protein myoglobin (Mb) using spectroscopic, calorimetric, ζ potential, and computational methods. Formation of a 1:1 complex between the ligand and Mb through well-defined equilibrium was observed. The binding constants obtained between Mb and SMZ/SDZ drugs were on the order of 104 M-1. SMZ with two additional methyl (-CH3) substitutions has higher affinity than SDZ. Upon drug binding, a notable loss in the helicity (via circular dichroism) and perturbation of the three-dimensional (3D) protein structure (via infrared and synchronous fluorescence experiments) were observed. The binding also indicated the dominance of non-polyelectrolytic forces between the amino acid residues of the protein and the drugs. The ligand-protein binding distance signified high probability of energy transfer between them. Destabilization of the protein structure upon binding was evident from differential scanning calorimetry results and ζ potential analyses. Molecular docking presented the best probable binding sites of the drugs inside protein pockets. Thus, the present study explores the potential binding characteristics of two sulfonamide drugs (with different substitutions) with myoglobin, correlating the structural and energetic aspects.

Dependence of the effective mass attenuation coefficient of gold nanoparticles on its radius.

PURPOSE: Several investigations are being carried since the past decade to use gold nanoparticles' (AuNP) suspensions as contrast agents (CA) for imaging in Computed Tomography. For this, the optimal size of AuNP has received considerable attention, which is addressed here. MATERIAL AND METHODS: In this theoretical study, effective attenuation coefficient for a single spherical shaped AuNP is first calculated from the first principles, as a function of the nanoparticle radius 'r', with µ(E) being the attenuation coefficient of the material for a given energy E. This result is extended to derive a formula for the attenuation coefficient and mass attenuation coefficient of a suspension of AuNP. RESULTS: It is seen that the effective mass attenuation coefficient of the nanoparticles is a decreasing function of α(E) = 2µ(E)r and falls inversely with α(E), for large values of α(E) ≫ 1, there being very little change for α ≤ 1. CONCLUSION: The paper shows that for nanoparticles, less than 100 nm in diameter the linear attenuation coefficient of the colloidal suspension has no dependence on the nanoparticles' size and depends only on the concentration of nanoparticle material present in the suspension.

COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy.

The COVID-19 pandemic has caused monumental mortality, and there are still no adequate therapies. Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. We speculate that the IL6-driven cytokine explosion plus hypoxemia causes a severe drop in Protein S level that exacerbates the thrombotic risk in COVID-19 patients. Here we highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and we suggest a path to therapy.

Biophysical and Thermodynamic Investigations on the Differentiation of Fluorescence Response towards Interaction of DNA: A Pyrene-Based Receptor versus Its Fe(III) Complex.

The Fe(III) complex [Fe(L)(NO3)(H2O)]+ (1) was prepared using a structurally characterized Schiff base ligand, 1-((pyren-1-ylimino) methyl) naphthalen-2-ol (HL), to develop an optical probe for fluorimetric recognition of DNA. An electrospray ionization-mass spectrometry (ESI-MS) study was carried out to ascertain the composition of 1 and the geometry of 1 was optimized by density functional theory (DFT) calculations. Compared to the strong intrinsic fluorescence of the ligand (HL), 1 was only weakly fluorescent. The interaction of 1 with DNA was investigated through different biophysical techniques. The fluorescence emission of 1 appeared to increase progressively in the presence of calf thymus (CT) DNA and this was utilized for the fluorimetric recognition of DNA. In comparison with 1, in the presence of DNA, the ligand HL showed quenching in its emission. The selectivity of 1 towards DNA was also confirmed in the presence of a large number of environmentally pertinent anions (NO3-, SO42-, Cl-, Br-, I-, OAC-, PO43-, ClO4-, HCO3-, H2PO4-, HPO42-, CO32-). Comprehensive DNA-binding experiments also showed that complex (1) and HL interacted with CT-DNA with different efficacies; the affinity of 1 was about six times higher than that of HL. Calorimetric studies showed that the 1-DNA association progressed with large positive entropy changes. In contrast, the association of HL with DNA was an enthalpy-driven process. Molecular docking results confirmed that the binding of 1 with CT-DNA progressed by intercalation and other noncovalent interactions.

Fluorescent ZnO-Au Nanocomposite as a Probe for Elucidating Specificity in DNA Interaction.

In this work, we report the interaction of a fluorescent ZnO-Au nanocomposite with deoxyribonucleic acid (DNA), leading to AT-specific DNA interaction, which is hitherto not known. For this study, three natural double-stranded (ds) DNAs having different AT:GC compositions were chosen and a ZnO-Au nanocomposite has been synthesized by anchoring a glutathione-protected gold nanocluster on the surface of egg-shell-membrane (ESM)-based ZnO nanoparticles. The ESM-based bare ZnO nanoparticles did not show any selective interaction toward DNA, whereas intrinsic fluorescence of the ZnO-Au nanocomposite shows an appreciable blue shift (Δλmax = 18 nm) in the luminescence wavelength of 520 nm in the presence of ds calf thymus (CT) DNA over other studied DNAs. In addition, the interaction of the nanocomposite through fluorescence studies with single-stranded (ss) CT DNA, synthetic polynucleotides, and nucleobases/nucleotides (adenine, thymine, deoxythymidine monophosphate, deoxyadenosine monophosphate) was also undertaken to delineate the specificity in interaction. A minor blue shift (Δλmax = 5 nm) in the emission wavelength at 520 nm was observed for single-stranded CT DNA, suggesting the proficiency of the nanocomposite for discriminating ss and ds CT DNA. More importantly, fluorescence signals from the nano-bio-interaction could be measured directly without any modification of the target, which is the foremost advantage emanated from this study compared with other previous reports. The AT base-pair-induced enhancement was also found to be highest for the melting temperature of CT DNA (ΔTmCT = 6.7 °C). Furthermore, spectropolarimetric experiments followed by calorimetric analysis provided evidence for specificity in AT-rich DNA interaction. This study would lead to establish the fluorescent ZnO-Au nanocomposite as a probe for nanomaterial-based DNA-binding study, featuring its specific interaction toward AT-rich DNA.

Egg-shell derived carbon dots for base pair selective DNA binding and recognition.

The development of base pair selective fluorescent binding probes and their interaction mode with nucleic acids have created great interest for sensing and biomedical applications. Herein, we have used chicken egg shell membrane (ESM) as a cost effective easily available protein source for the synthesis of highly fluorescent carbon dots. The detailed characterizations have confirmed the in situ formation of heteroatom doped graphitic carbon nanodots (CDs) from ESM. The intrinsic fluorescence property of the material has been utilized for the label free binding of duplex deoxyribonucleic acid (DNA). The interaction of different natural and synthetic DNAs with carbon dots resulted in the enhancement of fluorescence characteristics of the latter. Analysis of the binding data obtained from steady state fluorescence studies revealed a selective and stronger affinity of CDs to the adenine-thymine (AT) base pair rich double stranded DNA (ds DNA) than that of the guanine-cytosine (GC) pair rich ds DNA. Base pair specific binding was further validated from isothermal titration calorimetry (ITC) and melting temperature data. The thermodynamic profile revealed endothermic binding that was driven by the hydrophobic interaction at the nano-bio interfaces. The results reveal the potential of carbon dots as a new and promising fluorescent probe for base pair selective and sequence specific DNA recognition.

Non-invasive characterization of coronary artery atherosclerotic plaque using dual energy CT: Explanation in ex-vivo samples.

PURPOSE: In this study non-calcified plaque composition is evaluated by Dual Energy CT (DECT). Energy Dispersive X-ray Spectroscopy (EDS) has been used to study the Plaque composition. An attempt has been made to explain the DECT results with EDS analysis. METHODS: Thirty-two ex-vivo human cadaver coronary artery samples were scanned by DECT and data was evaluated to calculate their effective atomic number and electron density (Zeff & ρe) by inversion method. Result of DECT was compared with pathology to assess their differentiating capability. The EDS study was used to explain DECT outcome. RESULTS: DECT study was able to differentiate vulnerable plaque from stable with 87% accuracy (area under the curve (AUC):0.85 [95% confidence interval {CI}:0.73-0.98}] and Kappa Coefficient (KC):0.75 with respect to pathology. EDS revealed significant compositional difference in vulnerable and stable plaque at p < .05. The weight percentage of higher atomic number elements like F, Na, Mg, S, Si, P, Cl, K and Ca was found to be slightly more in vulnerable plaques as compared to a stable plaque. EDS also revealed a significantly increased weight percentage of nitrogen in stable plaques. CONCLUSIONS: The EDS results were able to explain the outcomes of DECT study. This study conclusively explains the physics of DECT as a tool to assess the nature of non-calcified plaques as vulnerable and stable. The method proposed in this study allows for differentiation between vulnerable and stable plaque using DECT.

A new insight into the interaction of ZnO with calf thymus DNA through surface defects.

Experimental evidences on the binding interaction of ZnO and Calf Thymus (CT) DNA using several biophysical techniques are the centre of interest of the present study. The interaction of ZnO with CT DNA has been investigated in detail by absorption spectral study, fluorescence titration, Raman analysis, zeta potential measurement, viscometric experiment along with thermal melting study and microscopic analysis. Steady-state fluorescence study revealed the quenching (48%) of the surface defect related peak intensity of ZnO on interaction with DNA. The optimized concentration of ZnO and DNA to obtain this level of quenching has been found to be 0.049mM and 1.027µM, respectively. Additional fluorescence study with 8-hydroxy-5-quinoline (HQ) as a fluorescence probe for Zn2+ ruled out the dissolution effect of ZnO under the experimental conditions. DNA conjugation on the surface of ZnO was also supported by Raman study. The quantitative variation in conductivity as well as electrophoretic mobility indicated significant interaction of ZnO with the DNA molecule. Circular dichroism (CD) and viscometry titrations provided clear evidence in support of the conformational retention of the DNA on interaction with ZnO. The binding interaction was found to be predominantly entropy driven in nature. The bio-physical studies presented in this paper exploring ZnO-CT DNA interaction could add a new horizon to understand the interaction between metal oxide and DNA.

Curcumin stably interacts with DNA hairpin through minor groove binding and demonstrates enhanced cytotoxicity in combination with FdU nucleotides.

We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV-Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two É£ H of curcumin heptadiene chain are closely positioned to the A16-H8 and A17-H8, while G12-H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy.

Thionine Conjugated Gold Nanoparticles Trigger Apoptotic Activity Toward HepG2 Cancer Cell Line.

Cancer cells were locally damaged using targeted gold nanoparticles (GNP) conjugated with therapeutic dye thionine (TN). GNP was prepared by citrate reduction method, and the two complexes, namely GTN1 and GTN2, were synthesized by mixing GNP and TN at different ratios at room temperature and at 80 °C, respectively. It is expected that GTN1 is formed when stabilizer TN participates in the reduction of Au3+ ions to Au0 nanocrystallites, while GTN2 is synthesized when the cationic dye TN adsorbs onto the GNP surfaces due to the electrostatic attraction. The compounds were characterized by strong plasmon resonance absorption, Fourier transform infrared spectroscopy, dynamic light scattering technique, ζ-potential measurement, transmission electron microscopy, and atomic force microscopy. Crystallinity of the NPs was ascertained by X-ray diffraction. Strong binding of GTN1 to DNA and the structural perturbation prompted us to study the cytotoxic activity of the compounds on hepatocellular carcinoma cell lines (HepG2) by MTT assay. The mode of cytotoxicity was found due to reactive oxygen species (ROS) generation inside the cells. Fluorescence microscopy analysis revealed nuclear fragmentation which was caused due to the ROS. The GTN1 induced fragmentation led to the apoptosis mediated cell death as found from the cell cycle study. Conclusions drawn from these studies emphasized GTN1 to be capable of inhibiting proliferation in cancer cells in an amount greater than that of other compounds. The importance of the work lies in the exploration of effectiveness of nanoparticles to prevent cancer cell proliferation, which is a progressive step toward novel biomedical applications.

Targeting human telomeric G-quadruplex DNA with antitumour natural alkaloid aristololactam-ß-D-glucoside and its comparison with daunomycin.

Study on anticancer agents that act via stabilization of telomeric G-quadruplex DNA has emerged as novel and exciting field for anticancer drug discovery. The interaction of carbohydrate containing anticancer alkaloid aristololactam-ß-D-glucoside (ADG) with human telomeric G-quadruplex DNA sequence was characterized by different biophysical techniques. The binding parameters were compared with daunomycin (DAN), a well-known chemotherapeutic drug. The Scatchard binding isotherms revealed noncooperative binding for both with the binding affinity values of (1.01 ± 0.05) × 106 and (1.78 ± 0.18) × 106 M-1 for ADG and DAN, respectively. Circular dichroism, ferrocyanide quenching study, anisotropy study, thiazole orange displacement, optical melting, differential scanning calorimetry study, and molecular docking study suggest significant stacking and stabilizing efficiency of ADG with comparison to DAN. The energetics of the interaction for ADG and DAN revealed that both reactions were predominantly entropy driven. Negative heat capacity values were obtained from the temperature dependence of the enthalpy change. The standard molar Gibbs energy change exhibited only marginal alterations with temperature suggesting the occurrence of enthalpy-entropy compensation. These findings indicate that ADG can act as a stabilizer of telomeric G-quadruplex DNA and thereby can be considered as a potential telomerase inhibitor.

Small molecule induced poly(A) single strand to self-structure conformational switching: evidence for the prominent role of H-bonding interactions.

All messenger RNAs (mRNAs) have a polyadenylic acid tail that is added during post transcriptional RNA processing. Investigation of the structure-function and interactions of polyadenylic acid is an important area to target for cancer and related diseases. Jatrorrhizine and coptisine are two important isoquinoline alkaloids that are structurally very similar, differing only in the substituents on the isoquinoline chromophore. Here we demonstrate that these alkaloids differentially induce a self-structure in single stranded poly(A) using absorbance, thermal melting and differential scanning calorimetry experiments. Jatrorrhizine was found to be more effective than coptisine in binding to poly(A) from spectroscopy and calorimetry data. Molecular modeling results suggested the involvement of more H-bonds in the complexation of the former with poly(A). It appears that the presence of substituents on the alkaloid that can form H-bonding interactions with the adenine nucleotides may play a critical role in the binding and structural rearrangement of poly(A) into the self-structure. The atomic force microscopy data directly visualized the poly(A) self-structured network. We propose a plausible mechanism of the small molecule induced self-structure formation in poly(A). The results presented here may help in the design of effective poly(A) targeted molecules for therapeutic use.

Selective Binding of Genomic Escherichia coli DNA with ZnO Leads to White Light Emission: A New Aspect of Nano-Bio Interaction and Interface.

Here, we report for the first time, a novel and intriguing application of deoxyribonucleic acid (DNA) in the area of optics by demonstrating white light emission by tuning the emission of a nanomaterial, ZnO rods, exhibiting surface defects, in the presence of genomic Escherichia coli DNA with a comparatively high quantum efficiency. In order to understand the DNA specificity, we have also studied the interaction of ZnO with CT, and ML DNA, ss EC DNA, synthetic polynucleotides and different mononucleosides and bases. Further, in order to understand the effect of particle shape and defects present in ZnO, we have also extended our study with ZnO rods prepared at higher temperature exhibiting red emission and ZnO particles exhibiting yellow emission. Interestingly, none of the above studies resulted in white light emission from ZnO-DNA complex. Our studies unequivocally confirmed that the concentration and the nature of DNA and ZnO together plays a crucial role in obtaining CIE coordinates (0.33, 0.33) close to white light. The much enhanced melting temperature (Tm) of EC DNA and the energetics factors confirm enhanced hydrogen bonding of ZnO with EC DNA leading to a new emission band. Our experimental observations not only confirm the selective binding of ZnO to EC DNA but also open a new perspective for developing energy saving light emitting materials through nano-bio interactions.

Visualization of Stepwise Drug-Micelle Aggregate Formation and Correlation with Spectroscopic and Calorimetric Results.

Palmatine and berberine, imperative isoquinoline alkaloids, have many potential therapeutic uses. We visualized the stepwise complex formation between these alkaloids and sodium dodecyl sulfate (SDS), a known anionic surfactant characterizing alkaloid-induced SDS micelle formation at different stages. UV-visible spectra directly divulged the complex formation at different stages, and this was supported by the fluorescence emission spectral and fluorescence anisotropy data. Fluorescence quenching experiments precisely located the alkaloid molecules in the micellar environment above the critical micelle concentration (CMC). The thermodynamics of the alkaloid binding and micelle formation suggested an exothermic enthalpy-driven initial electrostatic binding followed by an endothermic entropy-driven binding in the micellar core, both being spontaneous in nature. The atomic force microscopy results clearly visualized the shape and size of the alkaloid-induced micelles. This study presents stepwise characterization of alkaloid-SDS interaction below and above the CMC.

Design and application of Au decorated ZnO/TiO2 as a stable photocatalyst for wide spectral coverage.

A ternary nanostructured photocatalyst consisting of ZnO/TiO2/Au was designed to achieve an enhanced solar absorption due to the coupling of surface enhanced plasmonic absorption of metal and semiconductor excitons. TiO2 coated ZnO rods with an aspect ratio of 8-12 were decorated with citrate capped gold nanoparticles for photocatalytic degradation of organic pollutants in simulated waste water under solar irradiation. Simulated waste water was prepared so as to get a mixture exhibiting a wide range of spectral distribution in the UV-visible region by deliberately mixing congo red, methylene blue and malachite green. Photo-oxidation of few phenolic compounds such as phenol, 4-chlorophenol and polycyclic aromatic hydrocarbons viz. anthracene and phenanthrene were also investigated in order to rule out the visible light sensitization of the dye molecules and confirm the photocatalytic efficacy of the ternary composite for a wide range of water pollutants under simulated solar irradiation. The composite exhibited enhanced photocatalytic activity and photoelectrochemical stability upon UV and visible light exposure. This enhanced efficiency was also corroborated with the photocarrier lifetime and chronoamperometric studies. Under simulated solar irradiation, UV light induced well separated charge carriers coupled with the visible light induced local surface plasmon resonance of AuNPs to exert significantly enhanced photocatalytic activity in a broad spectral region. This type of material may evolve as a novel photocatalyst for the efficient removal of organic contaminants in waste water and photoelectrochemical water splitting under the solar spectrum.

Unraveling the Interaction of Silver Nanoparticles with Mammalian and Bacterial DNA.

The focus of this study was to understand and unravel the interaction of silver nanoparticles (AgNPs) with different types of Deoxyribonucleic acid (DNA), mammalian and bacterial, having different base pair compositions. Binding of spherical silver nanoparticles (AgNPs) to Calf thymus (CT) DNA, Escherichia coli (EC) DNA and Micrococcus lysodeikticus (ML) DNA has been studied to gain insights into their mode of interaction and specificity. Interaction of AgNPs with synthetic DNA has also been carried out. On the basis of absorption, thermal melting, isothermal calorimetry and viscosity studies, we could establish the mode of binding and specificity of the synthesized silver nanoparticles with mammalian and bacterial DNA. Thermal melting (Tm) studies indicated a decrease in the Tm of all the DNAs, confirming the destabilization of DNA stacks on interaction with AgNPs. Comparative interaction studies with single stranded (ss) and double stranded (ds) DNAs further confirmed the specificity of the particles toward ds DNA. On the basis of the results we could confirm that the synthesized AgNPs could be used for selective detection of DNA through their DNA binding mechanism. In addition, the AgNPs-DNA complexes exhibited distinct differences in the SERS spectra making it an interesting SERS platform for identifying ds DNA. The optical and physical properties of AgNPs help in differentiating the DNAs of different base pair compositions through their binding affinity and specificity.