Controlled Sequestration of DNA Intercalated Drug by Polymer–Surfactant Supramolecular Assemblies

Mora, Aruna K.; Singh, Prabhat Kumar; Nath, Sukhendu

doi:10.1021/acs.jpcb.5b12689

Cited by 16 publications

(21 citation statements)

References 59 publications

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“…The time-resolved emission measurements were performed using at ime-correlated single-photon counting (TCSPC)-based spectrometer from IBH, UK, as described earlier. [55] In time-resolved experiments, samples were excited with a3 40 nm LED source. The instrument response function (IRF) of the TCSPC instrument was 1.3 ns.…”

Section: Methodsmentioning

confidence: 99%

“…In steady‐state emission studies, 2Me‐DABT was excited at 340 nm to avoid the emission from insulin protein. The time‐resolved emission measurements were performed using a time‐correlated single‐photon counting (TCSPC)‐based spectrometer from IBH, UK, as described earlier . In time‐resolved experiments, samples were excited with a 340 nm LED source.…”

Section: Methodsmentioning

confidence: 99%

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Benzothiazole‐Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils

Mora

Murudkar

Alamelu

et al. 2016

Chemistry A European J

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Early detection of amyloid fibrils is very important for the timely diagnosis of several neurological diseases. Thioflavin-T (ThT) is a gold standard fluorescent probe for amyloid fibrils and has been used for the last few decades. However, due to its positive charge, ThT is incapable of crossing the blood-brain barrier and cannot be used for in vivo imaging of fibrils. In the present work, we synthesized a neutral ThT derivative, 2-[2'-Me,4'-(dimethylamino)phenyl]benzothiazole (2Me-DABT), which showed a strong affinity towards the amyloid fibrils. On association with the amyloid fibrils, 2Me-DABT not only showed a large increase in its emission intensity, but also, unlike ThT, a large blueshift in its emission spectrum was observed. Thus, unlike ThT, 2Me-DABT is a potential candidate for the ratiometric sensor of the amyloid fibrils. Detailed photophysical properties of 2Me-DABT in amyloid fibrils and different solvent media were studied to understand its sensory activity. Fluorescence resonance energy transfer (FRET) studies suggested that the sites of localization for ThT and 2Me-DABT in amyloid fibrils are not same and their average distance of separation in amyloid fibrils was determined. The experimental data was nicely supported by molecular docking studies, which confirmed the binding of 2Me-DABT in the inner core of the amyloid fibrils.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Benzothiazole‐Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils

Mora

Murudkar

Alamelu

et al. 2016

Chemistry A European J

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“…Below this CMC, SDS does not form a stable micelle in the solution. However, interestingly a neutral mixed micelle can be formed below this CMC value only in the presence of P123 . The midpoint of the sigmoidal fit to the absorption curves represents the melting temperature.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…Despite being a well-known chemotherapeutic, dose-dependent side effects of EPR-like irreversible cardiotoxicity restrict its clinical applications. , Hence, the removal of the excess drug (in the case of an overdose) or other mutagens from the off-target site is an important aspect of therapeutic applications. , In recent times, biocompatible supramolecular assembly systems have attracted considerable attention in anticancer therapy and for the removal of excess anticancer drugs from intercalated sites and off-target sites using the surfactant-based sequestration method. , Apart from passive targeting, ligand-modified polymeric micelles can be used for the selective targeting of cancer cells . For this reason, besides deciphering the EPR-MM DNA interaction mechanism, in this work, we have explored the sequestration of bound EPR from DNA binding sites using a mixed micellar system.…”

Section: Introductionmentioning

confidence: 99%

Preferential Binding of Epirubicin Hydrochloride with Single Nucleotide Mismatched DNA and Subsequent Sequestration by a Mixed Micelle

et al. 2021

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Targeting mismatched base pairs containing DNA using small molecules and exploring the underlying mechanism involved during the binding interactions is one of the fundamental aspects of drug design. These molecules in turn are used in nucleic acid targeted therapeutics and cancer diagnosis. In this work, we systematically delineate the binding of the anticancer drug, epirubicin hydrochloride (EPR) with 20-mer duplex DNA, having both natural nucleobase pairing and thermodynamically least stable non-Watson−Crick base pairing. From the thermal denaturation studies, we observed that EPR can remarkably enhance the thermal stability of cytosine-cytosine (CC) and cytosine-thymine (CT) mismatched (MM) DNA over other 20-mer duplex DNA. From steady-state fluorescence spectroscopy and isothermal titration calorimetry studies, we concluded that EPR binds strongly with the mismatched duplex DNA through the intercalation binding mode. The interaction of EPR and duplex DNA has also been monitored at a single molecular resolution using fluorescence correlation spectroscopy (FCS). Dynamic quantitates such as diffusion coefficients and hydrodynamic radii obtained from an FCS study along with association and dissociation rate constants estimated from intensity time trace analyses further substantiate the stronger binding affinity of EPR to the thermally less stable mismatched DNA, formed by the most discriminating nucleobase (viz. cytosine). Additionally, we have shown that EPR can be sequestered from nucleic acids using a mixed micellar system of an anionic surfactant and a triblock copolymer. From thermal denaturation studies and circular dichroism spectroscopy, we found that the extent of drug sequestration depends on the binding affinity of EPR to the duplex DNA, and this mixed micellar system can be employed for the removal of excess drug in the case of a drug overdose.

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“…The other type of polymer systems where the nanoscale segregation is common and actively studied nowadays is mixtures of polymers and surfactants. − Such systems are widely used in different applications for the stabilization of dispersed systems, the removal of metal anions from aqueous solutions, health care, controlled sequestration of drugs, enhanced oil recovery and hydraulic fracturing, food science, and cosmetics. ,,− Polymer–surfactant complexes can be used for the catalysis and for the synthesis of polymer microparticles as well. , …”

Section: Introductionmentioning

confidence: 99%

Surfactant-Induced Patterns in Polymer Brushes

Larin

Govorun

2017

Langmuir

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The properties of surfaces with grafted macromolecules are determined by a fine structure of the macromolecular layer, whereas the mixtures of macromolecules with surfactants are very rich in structure types. Using the scaling mean-field theory, we consider the self-assembly in polymer brushes into various patterns induced by interactions with low-molecular surfactants. The interaction energies of the parts of a surfactant molecule with the polymer units are assumed to be greatly different. With increasing the grafting density, the formation of lamellae perpendicular to the grafting plane, a continuous layer with oblong or round pores, or a homogeneous brush is predicted. The driving force of the pattern formation is a gain in the interaction energy of surfactant molecules oriented at the lateral surfaces of lamellae or pores. The process of pore formation in a homogeneous brush caused by a temperature change at definite grafting densities is described as the first-order phase transition. It is accompanied by a stepwise extension of the brush and by orientational ordering of surfactant molecules. The transitions between the other patterns are of the second order. The thickness of lamellae and the distance between pores are approximately twice the surfactant molecule size except for the extremely high grafting densities. The diagrams of brush patterns are presented and discussed.

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Controlled Sequestration of DNA Intercalated Drug by Polymer–Surfactant Supramolecular Assemblies

Cited by 16 publications

References 59 publications

Benzothiazole‐Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils

Benzothiazole‐Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils

Preferential Binding of Epirubicin Hydrochloride with Single Nucleotide Mismatched DNA and Subsequent Sequestration by a Mixed Micelle

Surfactant-Induced Patterns in Polymer Brushes

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