ABSTRACT
We have developed an ultrasensitive gas-detection method based on the measurement of a differential capacitance of electrified ionic liquid (IL) electrode interfaces in the presence and absence of adsorbed gas molecules. The observed change of differential capacitance has a local maximum at a certain potential that is unique for each type of gas, and its amplitude is related to the concentration of the gas molecules. We establish and validate this gas-sensing method by characterizing SO2 detection at ppb levels with less than 1.8% signal from other interfering species (i.e., CO2, O2, NO2, NO, SO2, H2O, H2, and cyclohexane, tested at the same concentration as SO2). This study opens a new avenue of utilizing tunable electrified IL-electrode interfaces for selective sensing of molecules with a kinetic size resolution of 0.1 Å.
Subject(s)
Gases/analysis , Ionic Liquids/chemistry , Carbon Dioxide/analysis , Cyclohexanes/analysis , Electrodes , Hydrogen/analysis , Kinetics , Nitric Oxide/analysis , Nitrogen Dioxide/analysis , Oxygen/analysis , Sulfur Dioxide/analysis , Water/analysisABSTRACT
Gold nanoparticles (Au NPs) have attracted much attention due to their potential applications in nano-medicine. While numerous studies have quantified biomolecular adsorption to Au NPs in terms of equilibrium binding constants, far less is known about biomolecular orientation on nanoparticle surfaces. In this study, the binding of the protein α-synuclein to citrate and (16-mercaptohexadecyl) trimethylammonium bromide (MTAB) coated 12 nm Au NPs is examined by heteronuclear single quantum coherence NMR spectroscopy to provide site-specific measurements of protein-nanoparticle binding. Molecular dynamics simulations support the orientation assignments, which show N-terminus binding to the Au NP for citrate-capped NPs, and C-terminus binding for the MTAB-capped NPs.
ABSTRACT
PURPOSE: An oligonucleotide termed 'T-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. We have demonstrated that T-oligo can induce apoptosis in androgen independent prostate cancer cell line DU-145. In this report, we evaluate the use of star-shaped tetraspermine (SSTS) for delivery of T-oligo. METHODS: SSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU-145 cells was compared with spermine and branched polyethyleneimine (bPEI). Atomistic molecular dynamic (MD) simulations were conducted to understand binding and complexation of spermine and SSTS with T-oligo. Complexation was also determined using gel electrophoresis and SYBR gold assay. Complexes were characterized for size, cellular uptake and antiproliferative effect. RESULTS: SSTS exhibited significantly lower toxicity than spermine and bPEI. Its affinity towards T-oligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes (TONPs) with T-oligo. TONPs facilitated cellular uptake and nuclear accumulation of T-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for T-oligo alone. CONCLUSION: SSTS significantly enhanced therapeutic benefits associated with the use of T-oligo and can be developed as a delivery vehicle for its in-vivo therapeutic applications.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Carriers/chemistry , Edetic Acid/analogs & derivatives , Nanoparticles/chemistry , Oligonucleotides/pharmacology , Prostatic Neoplasms , Spermine/analogs & derivatives , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Cell Culture Techniques , Cell Line, Tumor , Cell Survival/drug effects , Drug Carriers/chemical synthesis , Edetic Acid/chemical synthesis , Edetic Acid/chemistry , Flow Cytometry , Humans , Male , Molecular Conformation , Molecular Dynamics Simulation , Oligonucleotides/administration & dosage , Oligonucleotides/pharmacokinetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Spermine/chemical synthesis , Spermine/chemistryABSTRACT
Here we report the preparation of poly(oligonucleotide) brush polymers and amphiphilic brush copolymers from nucleic acid monomers via graft-through polymerization. We describe the polymerization of PNA-norbornyl monomers to yield poly-PNA (poly(peptide nucleic acid)) via ring-opening metathesis polymerization (ROMP) with the initiator, (IMesH2)(C5H5N)2(Cl)2RuCHPh.1 In addition, we present the preparation of poly-PNA nanoparticles from amphiphilic block copolymers and describe their hybridization to a complementary single-stranded DNA (ssDNA) oligonucleotide.
Subject(s)
Oligonucleotides/chemistry , Peptide Nucleic Acids/chemistry , DNA/chemistry , DNA, Single-Stranded/chemistry , Magnetic Resonance Spectroscopy , Nanoparticles/chemistry , Polymerization , Polymers/chemistryABSTRACT
A variety of delivery vehicles use spermine as a polycationic component to form complexes with nucleic acids. Thus, we investigated the influence of molecular architecture, amine density, and molecular weight of oligospermines on its binding to nucleic acids. We report the synthesis of mono, bis, and tetraspermines with linear, cyclic, dendritic, and quatrefoil architecture. The effect of molecular weight was more pronounced in linear oligospermines than their cyclic counterparts. Oligospermines with similar amine density but different molecular architectures exhibited different binding profiles. Among all oligospermines evaluated, dendritic tetraspermine exhibited the highest binding affinity. Atomistic molecular dynamics simulations also indicated higher affinity for dendritic tetraspermine to siRNA than its linear counterpart suggesting the importance of spermine geometry in binding to nucleic acids. Importantly, dendritic tetraspermine was less toxic than linear tetraspermine, suggesting its potential in nucleic acid delivery.
