Munia Ganguli

Institute of Genomics and Integrative Biology | IGIB

The (R-X-R) motif-containing arginine-rich peptides are among the most effective cell-penetrating peptides. The replacement of amide linkages in the (R-X-R) motif by carbamate linkages as in (r-ahx-r)(4) or (r-ahx-r-r-apr-r)(2) increases the efficacy of such oligomers several-fold. Internalization of these oligomers in mammalian cell lines occurs b...

Designing of nanocarriers that can efficiently deliver therapeutic DNA payload and allow its smooth intracellular release for transgene expression is still a major constraint. The optimization of DNA nanocarriers requires thorough understanding of the chemical and structural characteristics of the vector-nucleic acid complexes and its correlation w...

Glycosaminoglycans (GAGs) expressed ubiquitously on the cell surface are known to interact with a variety of ligands to mediate different cellular processes. However, their role in the internalization of cationic gene delivery vectors such as liposomes, polymers, and peptides is still ambiguous and seems to be controlled by multiple factors. In thi...

Rare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy...

Nucleic acid-based drugs are changing the scope of emerging medicine in preventing and treating diseases. Nanoparticle systems based on lipids and polymers developed to navigate tissue-level and cellular-level barriers are...

Frostbite is a severe health condition that is manifested in situations where an individual is exposed to extreme cold conditions. Touching materials such as ice packs/ dry ice, or just being exposed to a low wind speed in air temperature below -15°C can result in a freeze-burn. The manifestations vary from a self-healing superficial burn (frostnip...

Chondroitin sulfate (CS) belongs to a class of molecules called glycosaminoglycans (GAGs). These are long, linear chains of polysaccharides comprising alternating amino sugars and hexuronic acid. Similar to other GAGs, CS is important in a multitude of biological activities. Alteration of CS levels has been implicated in several pathological condit...

In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous wit...

Nonviral gene delivery has seen major progress in the last two decades owing to facile synthesis, low toxicity, and ease of modification of nanocarriers that take nucleic acids to cells and tissues. Gene delivery nanocomplexes need to reach the target locations in significant amounts by overcoming multiple barriers. While the importance of nanocomp...

Aim: The present study was aimed at determining the antiproliferative, antioxidant, anti-inflammatory and antitumor activity of developed silymarin-nanostructured lipid carrier (NLC) gel. Materials & methods: B16 melanoma cell line and albino mice were used as ex vivo and in vivo models, respectively, to evaluate the aforementioned pharmacological...

Nucleic acid delivery to the eye is a promising treatment strategy for many retinal disorders. In this manuscript, retinal gene delivery with non-coated and chondroitin sulphate (CS) coated amphipathic and cationic peptides was tested. The transfection and gene knockdown efficiencies were evaluated in different retinal pigment epithelial (RPE) cell...

Amide- and carbamate-linked dendrimeric oligomers are reported as molecular transporters. They effectively complex with pDNA and transport it into cells at an efficiency superior to Lipofectamine, when complexation is carried out by incubation overnight. The carbamate-linked K2C is superior to amide-linked K2A; their pDNA complexes have very low as...

ZnO nanoparticles of different sizes were functionalized with an amphipathic peptide and its effect on nanoparticle stabilization and UV photoprotective activity was studied. The peptide modified nanoparticles exhibited lower aggregation, significant reduction in Zn2+ leaching in vitro and even inside the cells for smaller particle sizes, reduced p...

Oxidative stress response in bacteria is mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, these genetic factors are either absent or rendered non-functional in the human pathogen Mycobacterium tuberculosis (Mtb). Therefore, how Mtb organizes gen...

Glycosaminoglycans, both cell-surface and exogenous, can interfere with DNA delivery efficiency of non-viral carrier systems. In this work, we report an extensive comparative study to explore the effect of exogenously added chondroitin sulphate on biophysical characteristics, cellular uptake, transfection efficiency and intracellular trafficking of...

Zinc oxide nanoparticles of 60 nm were dispersed in PBS and 2 different ionic liquids- choline acetate, 1-Butyl-3-methylimidazolium chloride. These formulations were tested in 4 different strains- Escherichia coli, Bacillus cereus, Klebsiella pneumoniae, and Staphylococcus epidermidis. Out of these combinations, maximum efficiency was obtained for...

In this investigation, an attempt has been made to provide comparative insight into the structural integrity, mechanical strength and anti-bacterial properties of three different transition metal ions namely Ag, Cu and Fe doped mesoporous nanobioglass for bone tissue engineering. Comparative 29 Si NMR of the various bioglass samples was elucidated...

Oxidative stress response in bacteria is generally mediated through coordination between the regulators of oxidant-remediation systems ( e.g. OxyR, SoxR) and nucleoid condensation ( e.g. Dps, Fis). However, these genetic factors are either absent or rendered nonfunctional in the human pathogen Mycobacterium tuberculosis ( Mtb ). Therefore, how Mtb...

In this investigation, an attempt has been made to provide comparative insight into the structural integrity, mechanical strength and anti-bacterial properties of three different transition metal ions namely Ag, Cu and Fe doped mesoporous nanobioglass for bone tissue engineering. Comparative 29Si NMR of the various bioglass samples was elucidated f...

Amide- and carbamate-linked dendrimeric oligomers are reported as molecular transporters. They effectively complex with pDNA and transport it into cells at an efficiency superior to Lipofectamine, when complexation is carried...

Amide- and carbamate-linked dendrimeric oligomers are reported as molecular transporters. They effectively complex with pDNA and transport it into cells at an efficiency superior to Lipofectamine, when complexation is carried out by incubation overnight. The carbamate-linked K2C is superior to amide-linked K2A; their pDNA complexes have very low as...

Topical delivery of nucleic acids to skin has huge prospects in developing therapeutic interventions for cutaneous disorders. In spite of initial success, clinical translation is vastly impeded by the constraints of bioavailability as well as stability in metabolically active environment of skin. Various physical and chemical methods used to overco...

Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving...

Conventionally, oxidative stress response in bacteria is mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, Mycobacterium tuberculosis (Mtb) lacks these mechanisms. Therefore, how Mtb organizes genome architecture and regulates gene expression to...

The present study is focused on a simple execution in the applicability of non-toxic lower generation poly amidoamine (PAMAM) dendrimers as effective nano-vectors in targeted gene delivery to the skin. So far the first three lower generation (G1, G2 and G3) PAMAM dendrimers have been overlooked as nucleic acid therapeutics. In this study, we have f...

Melanin and related polydopamine hold great promise, however restricted fine-tunabilility limits their usefulness in biocompatible applications. In the present study, by taking a bio-mimetic approach, we synthesize peptide-derived melanin with a range of physicochemical properties. Characterization of these melanin polymers indicates that they exis...

Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to o...

MicroRNAs (miRNAs) are key regulators of gene expression. In the brain, vital processes like neurodevelopment and neuronal functions depend on the correct expression of microRNAs. Perturbation of microRNAs in the brain can be used to model neurodegenerative diseases by modulating neuronal cell death. Currently, stereotactic injection is used to del...

Topical delivery to the skin is an essential step in non-invasive application of nucleic acid therapeutics for cutaneous disorders. The barrier posed by different layers of the skin - stratum corneum on top followed by the viable epidermis below - makes it extremely challenging for large hydrophilic molecules like nucleic acids to efficiently enter...

Arginine-rich peptides have been used extensively as efficient cellular transporters. However, gene delivery with such peptides requires development of strategies to improve their efficiency. We had earlier demonstrated that addition of small amounts of exogenous glycosaminoglycans (GAGs) like heparan sulfate or chondroitin sulfate to different arg...

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligo...

Delivery of DNA to cells remains a key challenge towards development of gene therapy. A better un-derstanding of the properties involved in stability and transfection efficiency of the vector could critically contribute to the improvement of delivery vehicles. In the present work we have chosen two peptides differing only in amphipathicity and expl...

The success of gene therapy relies on the development of safe and efficient multifunctional carriers of nucleic acids that can overcome extra- and intracellular barriers, protect the nucleic acid and mediate its release at the desired site allowing gene expression. Peptides bear unique properties that are indispensable for any carrier, e.g., they c...

We report, for the first time, bio-inspired synthesis of a bioactive glass-ceramic with superior textural properties in atmospheric conditions using CT-DNA as template. The phase composition, structure, morphology, and textural properties of the bioactive glass sample were evaluated with various analytical techniques before and after in vitro tests...

The bacterial chromosomal DNA is folded into a compact structure called as ‘nucleoid’ so that the bacterial genome can be accommodated inside the cell. The shape and size of the nucleoid are determined by several factors including DNA supercoiling, macromolecular crowding and nucleoid associated proteins (NAPs). NAPs bind to different sites of the...

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Amphipathic peptides constitute a class of molecules with the potential to develop as efficient and safer alternatives to viral and other nonviral vectors for intracellular delivery of therapeutics. These peptides can be useful for nucleic acid delivery and hence promise to have pharmaceutical application, particularly in gene therapy. In order to...

Amphipathic peptides constitute a class of molecules with the potential to develop as efficient and safer alternative to viral and other non-viral vectors for intracellular delivery of therapeutics. These peptides can be useful for nucleic acid delivery and hence promise to have pharmaceutical application, particularly in gene therapy. In order to...

The role of cell surface and exogenous glycosaminoglycans (GAGs) in DNA delivery by cationic peptides is controlled to a large extent by the peptide chemistry and the nature of its complex with DNA. We have previously shown that complexes formed by arginine homopeptides with DNA adopt a GAG-independent cellular internalization mechanism and show en...

In the present study, a novel strategy was adopted to synthesize, β lactamase resistant penicillin G molecules by using the unique properties of silver nanoparticles. Ascorbic acid-stabilized spherical monodispersed silver nanoparticles were prepared by a simple chemical reaction. The formation processes of the silver nanoparticles were investigate...

Amphipathic peptides with unusual cellular translocation properties have been used as carriers of different biomolecules. However, the parameters which control the delivery efficiency of a particular cargo by a peptide and the selectivity of cargo delivery are not very well understood. In this work, we have used the known cell penetrating peptide p...

Leishmania actin (LdACT) is an unconventional form of eukaryotic actin in that it markedly differs from other actins in terms of its filament forming as well as toxin and DNase-1-binding properties. Besides being present in the cytoplasm, cortical regions, flagellum and nucleus, it is also present in the kinetoplast where it appears to associate wi...

For more than two decades, gene therapy has sought to treat diseases with a genetic component. The eye is a promising target organ for gene therapy because of its unique features like easy accessibility and convenient methods of direct assessment of visual function as an effect of therapy. Several retinal diseases have been linked to specific genes...

The current study investigates the performance of polyelectrolyte complexes based nanoparticles in improving the antinociceptive activity of cationic chimeric peptide-YFa at lower dose. Size, Zeta potential and morphology of the nanoparticles were determined. Size of the nanoparticles decreases and zeta potential increases with concomitant increase...

Apicomplexans, including the pathogens Plasmodium and Toxoplasma, carry a nonphotosynthetic plastid of secondary endosymbiotic origin called the apicoplast. The P. falciparum apicoplast contains a 35 kb, circular DNA genome with limited coding capacity that lacks genes encoding proteins for DNA organization and replication. We report identification...

Peptides are emerging as attractive alternatives to cationic polymers and lipids for nonviral DNA delivery. Their remarkable properties such as efficient condensation of DNA, translocation across the cellular membrane, pH-sensitive membrane disruption, and efficient targeting of attached cargoes to the nucleus make them lucrative for researchers to...

Cationic poly(aminoacids) like poly-L-lysine (PLL) are known to be efficient in condensing plasmid DNA into compact nanostructures and have been used for in vitro and in vivo delivery of therapeutic DNA. Our study emphasizes on understanding the molecular mechanism of PLL-induced DNA condensation and the factors controlling it by visualization usin...

Bacillus anthracis makes highly stable, heat-resistant spores which remain viable for decades. Effect of various stress conditions on sporulation in B. anthracis was studied in nutrient-deprived and sporulation medium adjusted to various pH and temperatures. The results revealed that sporulation efficiency was dependent on conditions prevailing dur...

The crystal packing of arginine molecule shown in sphere model. The yellow color indicates the hydrophobic regions of arginine and the solvent molecules were shown in orange color. The coordinates were taken from Karle and Karle (see ref) and visualized using the program Mercury (Version 1.4). The view is along the b-axis. (0.17 MB TIF)

AFM images of Aβ1-42 in the presence of 0.2 M amino acids. (A) methionine after 24 h; (B) leucine after 24 h; (C) lysine after 24 h. (D) arginine after 48 h. Only arginine prevents Aβ1-42 aggregation significantly. Legend as in the figure 5. (2.45 MB TIF)

Mass spectra of methionine, lysine, leucine and proline. 0.2 M solutions in PB were used. The scan conditions were the same as used for arginine (Figure 2). (A) methionine, (B) lysine and (C) leucine do not display higher order clustering as proline (D) or arginine (Figure 2). (9.27 MB TIF)

ANS fluorescence in presence of arginine, methionine, lysine and leucine. The excitation wavelength was 400 nm. ANS fluorescent intensity was measured at the emission λmax for the respective amino acids at different concentrations. ANS was present at 250 µM concentration. The amino acids of respective concentration formed the control. Legend as in...

Protein precipitation is a process commonly observed during bacterial expression of heterologous proteins. The high concentration of currently used solubilizing agents limits the scope of purification procedures. Protein solubilizers acting at very low concentrations will allow function-based purification protocols. Such applications are possible w...

Atomic force microscopy (AFM) has been used to visualize the process of condensation of plasmid DNA by poly-L-ornithine on mica surface. AFM images reveal that the transition of negatively charged DNA to condensed nanoparticles on addition of increasing amounts of positively charged poly-L-ornithine (charge ratio (Z+/Z-) varied between 0.1 and 1) a...

Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on...

A novel class of hyperbranched polymers based on polyglycerol (PG) and poly(ethylene glycol) (PEG) are synthesized by multibranching anionic ring opening polymerization. Multivalent cationic sites are added to these polymers by a post-amination and quarternization reactions. Blood compatibility studies using these polymers at different concentratio...

The positive charge on PEI was partially shielded by forming ionic nanocomposites with a polysaccharide, alginic acid, in aqueous solution, bypassing tedious chemical synthesis. The content of alginic acid was varied systematically to obtain a series of nanocomposites. The nanocomposites were first characterized by assessing the surface charge (zet...

Recent advances in understanding biological systems have proven that RNA is not merely the carrier of genetic information, but also a key molecule in regulation of gene expression and other crucial metabolic processes. Therefore, it is being considered as an ideal therapeutic candidate both for metabolic and genetic disorders. However, research inv...

Cationic peptides self assemble upon interacting with sodium salt of oppositely charged polymer, poly(acrylic acid), PAA, giving rise to water-soluble nanoparticles at very low concentration (0.1 mM of PAA). The morphology of these kinds of nanoparticles is mainly governed by the composition of the complexes, which can be expressed as Z+/-, i.e., t...

External and internal changes occurring during the process of germination of Bacillus anthracis spores were observed through atomic force microscopy (AFM) and transmission electron microscopy (TEM), respectively. AFM studies showed that in response to L-alanine (4 mM), as a germinant, the spore germinates into a vegetative cell in 3 hours. The temp...

Atomic force microscopy has been used for direct visualization of the wrapping of DNA around 30-nm-sized functionalized gold nanoparticles for the first time. The morphology of the complexes seems to be dictated by the relative concentration of the nanoparticles and DNA. A higher concentration of the former leads to the formation of a network of na...

Lithium ion conductivity has been investigated in a boro-tellurite glass system, LiCl.LiBO2.TeO2. In the absence of LiCl, the conductivity increases with increasing non-bridging oxygen (NBO) concentration. LiCl addition has little influence on total conductivity although the observed barriers are low. Formation of LiCl clusters appears evident. In...

Complete biophysical characterization of complexes (polyplexes) of cationic polymers and DNA is needed to understand the mechanism underlying nonviral therapeutic gene transfer. In this article, we propose a new series of synthesized random cationic polymers (RCPs) from methoxy poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylam...

Glasses of the composition 30(Li,Na)2O·xB 2O3·(70-x) TeO2 (20 ≤ x ≤ 50) have been prepared using the melt-quenching method. Properties of these glasses have been measured and examined for the presence of mixed alkali effect (MAE). Infrared, Raman and 11B HR MAS NMR spectroscopies have been used to investigate the structure of these glasses. DC and...

DNA by virtue of its superlative ability to self-assemble has found use beyond biological research in the design and fabrication of nanomaterials. However, developing novel DNA-based materials for chemical applications might be restricted due to the insoluble nature of DNA in most common organic solvents. In this Communication, we are reporting the...

Na+ ion conductivity has been studied in SnO·NaPO3 glasses, which have been prepared over a wide range of compositions using a microwave melting technique. D.c. activation barriers seem to reflect the structural changes in system. A.c. conductivity analysis has revealed that while the power law exponent, s, seem to bear correlation to the structur...

As mentioned in Chapter 1, there can be thousands of molecules with polar heads and nonpolar tails, usable as surfactants. The applications are also many. Thus, the commercial anionic surfactants, recording about 50% of all surfactant production, are literally “used all over the place”: shampoos, dishwashing detergents and washing powders are some...

We have now come to the stage of this book where it is proposed to make an extensive survey of the experiments carried out in different laboratories on the synthesis of nanoparticles via microemulsions. It will be noted by the reader that a situation has been built up through the Chapters 1–3 where the basic issues involved in particle synthesis, e...

An essential feature of any emulsion is that it is at least a bi-component, bi-phasic substance. The simplest of emulsions are water droplets dispersed in some kind of an “oil” (water-in-oil or W/O) and the reverse (oil-in-water or O/W). An emulsion, thus, has at least a dispersed and a continuous or bulk phase.

Quite early in the history of studies on micelle formation, it was understood that the core of a micelle could take other substances. This involves the term “solubilization” which was defined as a method of “bringing into solution substances that are otherwise insoluble in a given medium” [1]. It may not be difficult to appreciate that the concept...

It should be amply evident from the accounts of Chapters 1–5 that assisted by well-established basic observations, various investigators have utilized both macro-and microemulsion processes for the synthesis of a large variety of inorganic substances in particulate form. The activity is more pronounced in case of microemulsion-mediated synthesis fo...

Electrical conductivity and dielectric relaxation studies with a wide range of compositions of lithium ion conducting glasses belonging to the ternary glass system Li2SO4–Li2O–B2O3 have been carried out over the temperature range 150–450 K and between 10–107 Hz. DC conductivities exhibit two different activation regions. This seems to suggest the p...

A wide range of compositions of glasses in the ternary Li2O–PbO–B2O3 glass system was prepared, and dc and ac conductivity measurements were carried out on these glasses. The presence of lead leads to a decrease in dc conductivities and an increase in the activation energies. This is likely to be due to the increase of the partial charges on the ox...

Electrical conductivity and dielectric relaxation studies on a large number of lithium ion conducting glasses belonging to the ternary glass system Li2SO4–Li2O–P2O5 have been carried out over a wide range of temperature (150 K to 450 K) and frequencies (10 Hz–107 Hz). DC conductivities exhibit two different activation regions. This seems to be sugg...

There is a renewed interest in the investigation of glasses which have potential as electrolytes for lithium batteries. Thermal and spectroscopic studies have been carried out on a number of glasses with wide ranging compositions in the pseudoternary glass system Li{sub 2}O-PbO-B{sub 2}O{sub 3} in order to understand the structural role of PbO in t...

Use of microwaves in the synthesis of materials is gaining importance. Microwave-assisted synthesis is generally much faster, cleaner, and more economical than the conventional methods. A variety of materials such as carbides, nitrides, complex oxides, silicides, zeolites, apatite, etc. have been synthesized using microwaves. Many of these are of i...

Thermal and spectroscopic investigations have been carried out on a number of glasses with a wide range of compositions in the pseudoternary glass system, LiâSOâ-LiâO-BâOâ, to understand the role of sulfate ions in modifying the borate glass structure. Both nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results indicate that four-...

Glasses in a wide range of compositions in the ternary system xLi2SO4–yLi2O–zP2O5 where x ranges from 0 to 30 mol%, y ranges from 35 to 55 mol% and z ranges from 25 to 50 mol% have been prepared and their properties measured using infra-red, Raman, and 31P magic angle spinning nuclear magnetic resonance spectroscopic techniques. We conclude that a...

Glasses in a wide range of compositions in the ternary system xLi2SO4–yLi2O–zP2O5 where x ranges from 0 to 30 mol%, y ranges from 35 to 55 mol% and z ranges from 25 to 50 mol% have been prepared and their properties measured using infra-red, Raman, and 31P magic angle spinning nuclear magnetic resonance spectroscopic techniques. We conclude that a...