Sudipta Panja

A single source-precursor route for the one-pot synthesis of highly luminescent CdS quantum dots as ultra-sensitive and selective photoluminescence sensor for Co2+ and Ni2+ ions

In this study, we have demonstrated a facile, simple one-pot and low cost method for the synthesis of 3-mercaptopropionic acid (MPA)-capped, water-soluble CdS quantum dots (QDs) with highly tunable optical properties. Initially Cd2+ coordinates with MPA at about pH 5, and the CdS QDs were then formed at a higher pH (7–12) under refluxing conditions through the disruption of coordination interaction with the release of sulfur. Here MPA played a dual role, as both, a source of sulfur and as a stabilizer. The particle size and the optical properties of the as-prepared CdS QDs were found to be dependent on the refluxing time for a given concentration ratio of the reactants and pH of the initial mixture. The broadness and large Stokes shift of emission of MPA–CdS QDs are due to the surface-trap state photoluminescence (PL). The PL peak around 510 nm–650 nm is due to the recombination of shallow trapped electrons in sulfur vacancy defect states with holes in the valence band, and a ∼665 nm peak (shoulder) arises from deep-trap states. The origin of the longer lifetime is presumed to be due to the involvement of surface-trap states and their environment. Use of MPA as a capping agent eventually enhances the water solubility as well as the stability of CdS QDs, which makes them useful for the ultra-sensitive detection of Co2+ and Ni2+. The selective coordination interaction of Co2+ and Ni2+ with MPA–CdS QDs through the carboxyl group of MPA provides a turn-off photoluminescence-based assay for sensitive detection of these metal ions without any interference of other commonly coexisting metal ions. The limit of detection (LOD) is 10 nM for Co2+ ions and 50 nM for Ni2+ ions. Co2+-induced color (from colorless to yellow) and UV-vis spectral change of MPA–CdS QDs is the simple way to distinguish Co2+ from Ni2+ in a higher concentration range (more than 5 µM). On the other hand the lower stability of the Co(II)–MPA complex than the Ni(II)–MPA complex provides a disodium salt of ethylenediaminetetraacetic acid (EDTA)-induced, time dependent turn-on photoluminescence-based technique to distinguish Co2+ from Ni2+ in the entire range of concentrations. EDTA-induced time dependent PL recovery of MPA–CdS QDs occurs via rapid dissociation of Co2+ ions from the surface of QDs than that of Ni2+. Thus our synthesized MPA–CdS QDs offer a very simple, rapid, cost-effective, turn-off–on photoluminescence-based technique for ultra-sensitive and selective detection of either Co2+ or Ni2+ in aqueous solution without interference of other common metal ions.

One pot green synthesis of graphene–iron oxide nanocomposite (GINC): an efficient material for enhancement of thermoelectric performance

We report for the first time, a green method for graphene–iron oxide nanocomposite (GINC) synthesis by dispersing graphene and nano iron oxide (Fe2O3) in ethanol via ultrasonication followed by micro-wave irradiation. This is a simple method of making a broader range of graphene–metal oxide nanocomposites with excellent dispersion of 3D nanoparticles over 2D graphene. In addition, we have also demonstrated the synthesis of highly conductive PVAc–GINC and PVAc–graphene composites by ultrasonication followed by hot compaction for thermoelectric application. Graphene and GINC concentration were judiciously varied and optimized for the sake of high electrical conductivity and Seebeck coefficient. The fabricated PVAc–GINC film exhibited a conductivity of 2.18 × 104 S m−1 with a Seebeck coefficient of 38.8 μV K−1. Hence, the power factor (PF) reaches 32.90 μW m−1 K−2, which is 27 fold higher than the thermoelectric material based on PVAc–graphene composite. This PF value is found to be the maximal ever reported without using conducting polymer.

Tailor-Made Temperature-Sensitive Micelle for Targeted and On-Demand Release of Anticancer Drugs

The design of nanomedicines from the tuned architecture polymer is a leading object of immense research in recent years. Here, smart thermoresponsive micelles were prepared from novel architecture four-arm star block copolymers, namely, pentaerythritol polycaprolactone-b-poly(N-isopropylacrylamide) and pentaerythritol polycaprolactone-b-poly(N-vinylcaprolactam). The polymers were synthesized and tagged with folic acid (FA) to render them as efficient cancer cell targeting cargos. FA-conjugated block copolymers were self-assembled to a nearly spherical (ranging from 15 to 170 nm) polymeric micelle (FA-PM) with a sufficiently lower range of critical micelle concentration (0.59 × 10(-2) to 1.52 × 10(-2) mg/mL) suitable for performing as an efficient drug carrier. The blocks show lower critical solution temperature (LCST) ranging from 30 to 39 °C with high DOX-loading content (24.3%, w/w) as compared to that reported for a linear polymer in the contemporary literature. The temperature-induced reduction in size (57%) of the FA-PM enables a high rate of DOX release (78.57% after 24 h) at a temperature above LCST. The DOX release rate has also been tuned by on-demand administration of temperature. The in vitro biocompatibilities of the blank and DOX-loaded FA-PMs have been studied by the MTT assay. The cellular uptake study proves selective internalization of the FA-PM into cancerous cells (C6 glioma) compared that into normal cells (HaCaT). In vivo administration of the DOX-loaded FA-PMs into the C6 glioma rat tumor model resulted in significant accumulation in tumor sites, which drastically inhibited the tumor volume by ∼83.9% with respect to control without any significant systemic toxicity.

Organic solvent-free low temperature method of preparation for self assembled amphiphilic poly(ϵ-caprolactone)-poly(ethylene glycol) block copolymer based nanocarriers for protein delivery.

Degradation and denaturation of labile biomolecules during preparation of micelles by organic solvent at high temperature are some of the limitations for fabrication of advanced polymer based protein delivery systems. In this paper, effectiveness of heat-chill method for preparation of micelles containing large labile biomolecules was investigated using insulin as a model protein molecule. Micelles (average size, <120 nm) were prepared using amphiphilic diblock and triblock copolymers of poly(ethylene glycol) (PEG) and poly(ϵ-caprolactone) (PCL). Micelles were prepared by heating PEG-PCL block copolymers with distilled water at 60 °C followed by sudden chilling in an ice-water bath. Effects of molecular architecture on morphology, stability and protein loading capacity of micelles were investigated. Micelles prepared using high molecular weight block copolymers exhibited good colloidal stability, encapsulation efficiency and insulin release characteristics. Insulin retained its secondary structure after micelles preparation as confirmed by CD spectroscopic study. Furthermore, in vitro cytotoxicity test suggested that the prepared micellar nanoparticles possessed biocompatibility. In a nut shell, heat-chill method of micellar nanoparticles preparation is well suited for encapsulating labile proteins and other allied biomolecules which degrade in presence of toxic organic solvents and at elevated temperatures.

Self-assembly of a biodegradable branched PE-PCL-b-PEC amphiphilic polymer: synthesis, characterization and targeted delivery of doxorubicin to cancer cells

A novel biodegradable branched block copolymer was synthesized by the ring-opening polymerization of ethylene carbonate using pre-synthesized four-armed pentaerythretol poly(e-caprolactone) (PE-PCL) as a macro initiator. Folic acid was conjugated with the end-group of the block copolymer and self-assembled in water to form polymer micelles (PMs). The very low critical micelle concentration of the block copolymer suggests its potential application in advanced drug delivery systems. The PMs are spherical in shape and have an average size of 80 nm, which is suitable for the delivery of drugs. The hydrophobicity of pentaerythretol poly(e-caprolactone) and its branched structure can accommodate high amounts of doxorubicin. Compared with a blank sample, PMs containing encapsulated doxorubicin show a much higher cytotoxicity towards HeLa cells. A high rate of release of doxorubicin in vitro at pH 5.0 shows that the system is responsive to pH. Confocal laser scanning microscopy showed that the doxorubicin-loaded PMs were internalized into the HeLa cells.

A Smart Magnetically Active Nanovehicle for on-Demand Targeted Drug Delivery: Where van der Waals Force Balances the Magnetic Interaction

The magnetic field is a promising external stimulus for controlled and targeted delivery of therapeutic agents. Here, we focused on the preparation of a novel magnetically active polymeric micelle (MAPM) for magnetically targeted controlled drug delivery. To accomplish this, a number of superparamagnetic as well as biocompatible hybrid micelles were prepared by grafting four armed pentaerythretol poly(ε-caprolactone) (PE-PCL) onto the surface of Fe3O4 magnetic nanoparticles (MNPs) of two different ranges of size (∼5 nm and ∼15 nm). PE-PCL (four-armed) was synthesized by ring-opening polymerization, and it has been subsequently grafted onto the surface of modified MNP through urethane (-NHCO-) linkage. Polymer-immobilized MNP (5 and 15 nm) showed peculiar dispersion behavior. One displayed uniform dispersion of MNP (5 nm), while the other (15 nm) revealed associated structure. This type of size dependent contradictory dispersion behavior was realized by taking the van der Waals force as well as magnetic dipole-dipole force into consideration. The uniformly dispersed polymer immobilized MNP (5 nm) was used for the preparation of MAPM. The hydrodynamic size and bulk morphology of MAPM were studied by dynamic light scattering and high-resolution transmission electron microscopy. The anticancer drug (DOX) was encapsulated into the MAPM. The magnetic field triggers cell uptake of MAPM micelles preferentially toward targeted cells compare to untargeted ones. The cell viabilities of MAMP, DOX-encapsulated MAPM, and free DOX were studied against HeLa cell by MTT assay. In vitro release profile displayed about 51.5% release of DOX from MAPM (just after 1 h) under the influence of high frequency alternating magnetic field (HFAMF; prepared in-house device). The DOX release rate has also been tailored by on-demand application of HFAMF.

Detailed scenario of the acid-base behavior of prototropic molecules in the subdomain-IIA pocket of serum albumin: results and prospects in drug delivery.

The protein pocket performs magically in controlling, inhibiting, or optimizing various biochemical processes. The elegant 3D disposition of different side chains in the cavity is a key point in accommodating specific ligands. Anion receptors in the subdomain-IIA pocket of serum albumin (SA) prefer to home anionic ligands. Acid-base behavior is an important property that relates to bioavailability and action of prototropic molecules/drugs. The present study provides a comprehensive understanding of the effect of subdomain-IIA pocket-specific interaction on the acid-base equilibrium of housed guests. The pKa of subdomain-IIA binder basic drugs decreases due to unfavorable interaction with the cationic drug species, while the decrease in the pKa of acidic drugs is due to favored binding of the deprotonated species presumably via electrostatic interaction with anion receptors. Acidity-shifting efficacy of albumins is introduced for the first time using the pKa-shifting index (α), a unique parameter for a given prototropic-drug-host pair to assess bioavailability. The acidic drug warfarin and the basic drug fuberidazole, showing a high α-value, should be efficient in drug-SA cocktail, and those with low α should be less efficient. Use of the pKa-shifting index for prototropy-based drugs should enable the drug efficacy to be evaluated smartly for similar systems. Shifting of the pKa of protein-encapsulated drugs stems the possibility of albumin-based delivery systems for extracting the therapeutically active species.

Exploration of electrostatic interaction in the hydrophobic pocket of lysozyme: Importance of ligand-induced perturbation of the secondary structure on the mode of binding of exogenous ligand and possible consequences.

Exogenous ligand binding can be adequate to alter the secondary structure of biomolecules besides other external stimuli. In such cases, structural alterations can complicate on the nature of interaction with the exogenous molecules. In order to accommodate the exogenous ligand, the biomolecule has to unfold resulting in a considerable change to its properties. If the bound ligand can be unbound, the biomolecule gets the opportunity to refold back and return to its native state. Keeping this in mind, we have purposely investigated the interaction of tartrazine (TZ), a well abundant azo food colorant, with two homologous lysozymes, namely, human lysozyme (HLZ) and chicken egg white lysozyme (CEWLZ) in physiological pH condition. The binding of TZ with lysozymes has been identified to accompany a ligand-induced secondary structure alteration as indicated by the circular dichroism spectra, and the reduction of α-helical content is more with HLZ than CEWLZ. Interestingly, the binding is identified to occur in the electronic ground state of TZ with lysozyme in its hydrophobic cavity, containing excess of positive charge, predominantly via electrostatic interaction. With increase of salinity of the medium the protein tends to refold back due to wakening of electrostatic forces and consequent reduction of strength of ligand interaction and unbinding. The entropy enthalpy compensation (EEC) has been probed to understand the binding features and it is found that CEWLZ-TZ shows better compensation than HLZ-TZ complex. This is presumably due to the fact that with CEWLZ the binding does not accompany substantial change in the protein secondary structure and hence ineffective to scramble the EEC. The present study initiates the importance of ligand-perturbed structural alteration of biomolecule in controlling the thermodynamics of binding. If there is a considerable alteration of the protein secondary structure due to binding, it is indicative that such changes should bring in the overall loss of activity of protein.

Reorganization energy and Stokes shift calculations from spectral data as new efficient approaches in distinguishing the end point of micellization/aggregation

Critical micellar concentration (CMC) is an important parameter which indicates the matured associated state of amphiphilic molecules. The present work demonstrates a new, accurate, and generalized method for the determination of the critical micellar concentration (CMC) based on the estimation of the reorganization energy (RE) and Stokes shift of fluorescent probes placed inside micellar aggregates. With increasing concentration of surfactant, the fluorophore is well portioned in the micellar environment. The change in the magnitude of the Stokes shift and reorganization energy with respect to bulk water is a result of the formation of aggregates from surfactant monomers and there is a substantial change of RE in the vicinity of the CMC like what is observed with various other physical parameters during micellization. CMC values determined from both Stokes shift calculation and reorganization energy estimations are comparable with those previously reported in the literature. However, we demonstrate that reorganization energy calculation provides improved consistency and is more user-friendly than that estimated from Stokes shift measurements.

Simultaneous Binding of Folic Acid and Methotrexate to Human Serum Albumin: Insights into the Structural Changes of Protein and the Location and Competitive Displacement of Drugs

Protein structure can be flexible to adopt multiple conformations to house small molecules. In this paper, we have attempted to experimentally figure out how the structure of a transport protein steer the drug–drug competition (DDC) by maintaining the equilibrium distribution of the bound and unbound fractions of drugs. This understanding is an important facet in biophysical and medicinal chemistry to ascertain the effectiveness of drugs. It is important to note that majority of studies involving small-molecule–transport protein interaction aimed at characterizing the binding process, and because these proteins can interact with thousands of molecules, there are hundreds of reports on such interactions. This ultimately led to an impression among the readers that any studies involving serum albumin may not lead to any new findings except for traditional binding explorations. However, in the present paper, we would like to draw the attention of the readers that our findings are very surprising, new, and important, involving the phenomenon of ligand–protein interaction. Here, we have studied two structurally similar drugs methotrexate (MTX) and folic acid (FA), which attempt to bind the primary binding site (subdomain IIA), one at a time, of human serum albumin. Details of binding analyses reveal that when both of the drugs are present, the single-site binding mode of FA prefers to occupy the primary binding site and hence pushes the primary-site-bound MTX to another location (subdomain IIIA), which is the second binding site of MTX. The structural analysis indicates that DDC has occurred in a cooperative fashion so that the loss of the protein secondary structure is minimum when both drugs are bound to the protein, which means that in the case of duo-drug binding, the conventional interaction between the drug and the protein is altered to undergo restoration of the protein structure. This can indeed regulate the DDC by modifying the bound and unbound fractions of MTX in plasma. The present study emphasizes that in vitro structural characterizations of the transport protein provide important information to improve the molecular-level understanding of DDC for further therapeutic applications with combination drug.