Subho Mozumdar

Lipid-based systemic delivery of siRNA ☆

RNAi technology has brought a new category of treatments for various diseases including genetic diseases, viral diseases, and cancer. Despite the great versatility of RNAi that can down regulate almost any protein in the cells, the delicate and precise machinery used for silencing is the same. The major challenge indeed for RNAi-based therapy is the delivery system. In this review, we start with the uniqueness and mechanism of RNAi machinery and the utility of RNAi in therapeutics. Then we discuss the challenges in systemic siRNA delivery by dividing them into two categories-kinetic and physical barriers. At the end, we discuss different strategies to overcome these barriers, especially focusing on the step of endosome escape. Toxicity issues and current successful examples for lipid-based delivery are also included in the review.

Biodegradable calcium phosphate nanoparticle with lipid coating for systemic siRNA delivery

A lipid coated calcium phosphate (LCP) nanoparticle (NP) formulation was developed for efficient delivery of small interfering RNA (siRNA) to a xenograft tumor model by intravenous administration. Based on the previous formulation, liposome-polycation-DNA (LPD), which was a DNA-protamine complex wrapped by cationic liposome followed by post-insertion of PEG, LCP was similar to LPD NP except that the core was replaced by a biodegradable nano-sized calcium phosphate precipitate prepared by using water-in-oil micro-emulsions in which siRNA was entrapped. We hypothesized that after entering the cells, LCP would de-assemble at low pH in the endosome, which would cause endosome swelling and bursting to release the entrapped siRNA. Such a mechanism was demonstrated by the increase of intracellular Ca(2+) concentration as shown by using a calcium specific dye Fura-2. The LCP NP was further modified by post-insertion of polyethylene glycol (PEG) with or without anisamide, a sigma-1 receptor ligand for systemic administration. Luciferase siRNA was used to evaluate the gene silencing effect in H-460 cells which were stably transduced with a luciferase gene. The anisamide modified LCP NP silenced about 70% and 50% of luciferase activity for the tumor cells in culture and those grown in a xenograft model, respectively. The untargeted NP showed a very low silencing effect. The new formulation improved the in vitro silencing effect 3-4 folds compared to the previous LPD formulation, but had a negligible immunotoxicity.

Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery

Calcium phosphate nanoparticles present a unique class of non-viral vectors, which can serve as efficient and alternative DNA carriers for targeted delivery of genes. In this study we report the design and synthesis of ultra-low size, highly monodispersed DNA doped calcium phosphate nanoparticles of size around 80 nm in diameter. The DNA encapsulated inside the nanoparticle is protected from the external DNase environment and could be used safely to transfer the encapsulated DNA under in vitro and in vivo conditions. Moreover, the surface of these nanoparticles could be suitably modified by adsorbing a highly adhesive polymer like polyacrylic acid followed by conjugating the carboxylic groups of the polymer with a ligand such as p-amino-1-thio-beta-galactopyranoside using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride as a coupling agent. We have demonstrated in our studies that these surface modified calcium phosphate nanoparticles can be used in vivo to target genes specifically to the liver.

Response speed of SnO2-based H2S gas sensors with CuO nanoparticles

CuO nanoparticles on sputtered SnO2 thin-film surface exhibit a fast response speed (14 s) and recovery time (61 s) for trace level (20 ppm) H2S gas detection. The sensitivity of the sensor (S∼2.06×103) is noted to be high at a low operating temperature of 130 °C. CuO nanoparticles on SnO2 allow effective removal of excess adsorbed oxygen from the uncovered SnO2 surface due to spillover of hydrogen dissociated from the H2S–CuO interaction.

The first Au-nanoparticles catalyzed green synthesis of propargylamines via a three-component coupling reaction of aldehyde, alkyne and amine

Recyclable Au-nanoparticles provide an efficient, economic, novel route for multi component A3 coupling reaction of aldehyde, amine and alkyne. This method provides the wide range of substrate applicability. This protocol avoids the use of heavy metals, co-catalyst and gives the propargylamine in excellent yields.

Copper nanoparticulates in Guar-gum: a recyclable catalytic system for the Huisgen [3 + 2]-cycloaddition of azides and alkynes without additives under ambient conditions

Cu-nanoparticulates in Guar-gum at room temperature were investigated for the first time as a recyclable catalytic system in organic synthesis. The catalytic potential of these materials were evaluated in the Huisgen [3 + 2]-cycloaddition of azides and alkynes without additives under ambient conditions which offers several advantages, viz. high yields, clean reactions, short reaction times, recyclability of the catalyst and a simple workup procedure.

Targeted Delivery of Pesticides Using Biodegradable Polymeric Nanoparticles

In the current scenario the persistent challenge is to produce more food and secure the cultivated food to feed the world. The green revolution has brought tremendous increase in the worldwide crop production. Protecting the growing crop and securing the yielded gains by using pesticide has additionally helped in the production. However, the amazing performance of pesticides has encouraged their excessive use and is now causing accumulation in the environment. It has been found that the residue of pesticides can contaminate soil, water, and through crops can enter the food chain. Over the past few years there has been an increasing pressure from government and regulatory authorities to develop formulations which can have less impact on the environment and be safe for nontargeted species. In this direction, conventional formulations like granules, emulsions, and suspensions are being continuously replaced by novel formulations like microemulsions and multiple-emulsions and further by upcoming nano-formulations. Nano-formulations have the advantage that less quantity of pesticide can be used to target large area and thereby made to exert lesser impact on pesticide accumulation in the environment. Moreover, selection of biologically nontoxic ingredient for nano-formulations can additionally ensure the safety of the products.

Cu Nanoparticles in PEG: A New Recyclable Catalytic System for N‐Arylation of Amines with Aryl Halides

A new protocol for the N‐arylation of aryl halides with anilines using Cu nanoparticles in polyethylene glycol (PEG) as an efficient and reusable catalytic system has been developed. The reaction did not require any cocatalyst. Various solvents were screened, and PEG400 provided the best results. The studies showed that the mechanism of catalytic action is dependent on the size of the nanoparticles. The Cu nanoparticles and PEG were recyclable and retained their activity. This newly developed protocol was also found to be suitable for the cross coupling of NH heterocycles with iodobenzene. The present methodology offers several advantages, such as excellent yields, short reaction times, and milder reaction conditions.

Controlled synthesis of size-tunable nickel and nickel oxide nanoparticles using water-in-oil microemulsions

Industrial demands have generated a growing need to synthesize pure metal and metal?oxide nanoparticles of a desired size. We report a novel and convenient method for the synthesis of spherical, size tunable, well dispersed, stable nickel and nickel oxide nanoparticles by reduction of nickel nitrate at room temperature in a TX-100/n-hexanol/cyclohexane/water system by a reverse microemulsion route. We determined that reduction with alkaline sodium borohydrate in nitrogen atmosphere leads to the formation of nickel nanoparticles, while the use of hydrazine hydrate in aerobic conditions leads to the formation of nickel oxide nanoparticles. The influence of several reaction parameters on the size of nickel and nickel oxide nanoparticles were evaluated in detail. It was found that the size can be easily controlled either by changing the molar ratio of water to surfactant or by simply altering the concentration of the reducing agent. The morphology and structure of the nanoparticles were characterized by quasi-elastic light scattering (QELS), transmission electron microscopy (TEM), x-ray diffraction (XRD), electron diffraction analysis (EDA) and energy dispersive x-ray (EDX) spectroscopy. The results show that synthesized nanoparticles are of high purity and have an average size distribution of 5?100?nm. The nanoparticles prepared by our simple methodology have been successfully used for catalyzing various chemical reactions.

Using Hydrophilic Ionic Liquid, [bmim]BF4 – Ethylene Glycol System as a Novel Media for the Rapid Synthesis of Copper Nanoparticles

In this work, we present a novel method for the synthesis of copper nanoparticles. We utilize the charge compensatory effect of ionic liquid [bmim]BF4 in conjunction with ethylene glycol for providing electro-steric stabilization to copper nanoparticles prepared from copper sulphate using hydrazine hydrate as a reducing agent. The formed copper nanoparticles showed extended stability over a period of one year. Copper nanoparticles thus prepared were characterized by powder X-ray diffraction measurements (pXRD), transmission electron microscopy (TEM) and quasi elastic light scattering (QELS) techniques. Powder X-ray diffraction (pXRD) analysis revealed relevant Braggs reflection for crystal structure of copper. Powder X-ray diffraction plots also revealed no oxidized material of copper nanoparticles. TEM showed nearly uniform distribution of the particles in methanol and confirmed by QELS. Typical applications of copper nanoparticles include uses in conductive films, lubrication and nanofluids. Currently efforts are under way in our laboratory for using these nanoparticles as catalysts for a variety of organic reactions.