Mohit S. Verma

Colorimetric biosensing of pathogens using gold nanoparticles

Rapid detection of pathogens is crucial to minimize adverse health impacts of nosocomial, foodborne, and waterborne diseases. Gold nanoparticles are extremely successful at detecting pathogens due to their ability to provide a simple and rapid color change when their environment is altered. Here, we review general strategies of implementing gold nanoparticles in colorimetric biosensors. First, we highlight how gold nanoparticles have improved conventional genomic analysis methods by lowering detection limits while reducing assay times. Then, we focus on emerging point-of-care technologies that aim at pathogen detection using simpler assays. These advances will facilitate the implementation of gold nanoparticle-based biosensors in diverse environments throughout the world and help prevent the spread of infectious diseases.

Size-tunable nanoparticles composed of dextran-b-poly(D,L-lactide) for drug delivery applications

AbstractNanoparticles (NPs) formulated using self-assembly of block copolymers have attracted significant attention as nano-scaled drug delivery vehicles. Here we report the development of a biodegradable NP using self-assembly of a linear amphiphilic block copolymer, Dex-b-PLA, composed of poly(D,L-lactide), and dextran. The size of the NPs can be precisely tuned between 15 and 70 nm by altering the molecular weight (MW) of the two polymer chains. Using doxorubicin as a model drug, we demonstrated that the NPs can carry up to 21% (w/w) of the drug payload. The release profile of doxorubicin from NPs showed sustained release for over 6 days. Using a rat model, we explored the pharmacokinetics profiles of Dex-b-PLA NPs, and showed proof-of-concept that long circulation lifetime of the NPs can be achieved by tuning the MW of Dex-b-PLA block copolymer. While the terminal half-life of Dex-b-PLA NPs (29.8 h) was similar to that observed in poly(ethylene glycol)-coated (PEG-coated) NPs (27.0 h), 90% of the injected Dex-b-PLA NPs were retained in the blood circulation for 38.3 h after injection, almost eight times longer than the PEG-coated NPs. The area under curve (AUC) of Dex-b-PLA NPs was almost four times higher than PEG-based NPs. The biodistribution study showed lower accumulation of Dex-b-PLA NPs in the spleen with 19.5% initial dose per gram tissue (IDGT) after 24 h compared to PEG-coated poly(lactide-co-glycolide) (PLGA) NPs (29.8% IDGT). These studies show that Dex-b-PLA block copolymer is a promising new biomaterial for making controlled nanoparticles as drug delivery vehicles.

Nanotechnology and Diagnostic Imaging: New Advances in Contrast Agent Technology

Medical imaging technologies allow for the rapid diagnosis and evaluation of a wide range of pathologies. In order to increase their sensitivity and utility, many imaging technologies such as CT and MRI rely on intravenously administered contrast agents. While the current generation of contrast agents has enabled rapid diagnosis, they still suffer from many undesirable drawbacks including a lack of tissue specificity and systemic toxicity issues. Through advances made in nanotechnology and materials science, researchers are now creating a new generation of contrast agents that overcome many of these challenges, and are capable of providing more sensitive and specific information. In this review, we summarize the main classes of nanotechnology-based contrast agents for each of the major imaging technologies, and highlight progress in their development as well as the challenges to be addressed. We also review the relevant biological interactions that determine the in vivo fate of these contrast agents, and describe major themes in medical nanotechnology including stealth and targeting.

Controlled root targeted delivery of fertilizer using an ionically crosslinked carboxymethyl cellulose hydrogel matrix

AimsThe recent increases in food prices caused by the corresponding increases in fertilizer costs have highlighted the demand for reducing the overuse of fertilizers in industrial agriculture. There has been increasing interest in developing plant root-targeted delivery (RTD) of fertilizers in order to address the problem of inefficient fertilizer use. The aim of this study is to develop a low cost controlled release device to deliver fertilizers to plant roots and thereby increase fertilizer use efficiency.MethodsThe Root Targeted Delivery Vehicle (RTDV) is formed by dissolving Carboxymethyl Cellulose (CMC) chains in water, mixing it with liquid fertilizer and crosslinking using iron and calcium salts. Basic measurements quantifying nutrient release and green house growth trials were carried out to evaluate fertilizer use efficiency on wheat growing in nutrient depleted soil media.ResultsGrowing wheat in nutrient depleted media showed that the RTDV permits a 78% reduction in the amount of fertilizer needed to achieve similar levels of plant yield in these conditions. Quantifying the losses associated with the RTDV synthesis showed that optimizing manufacturing could possibly increase this value as high as 94%. Furthermore, the delivery device showed a similar lifetime in soil to the plant’s growth cycle, delivering fertilizer over the course of the plant’s growth before removal from soil by degradation.ConclusionsThese results illustrate the importance of fertilizer delivery in facilitating absorption and may have potential to vastly increase the use efficiency of fertilizers in soil, resulting in a significant reduction of costs and environmental damage. With more in depth study to quantify the fertilizer release and refine the device, there is great potential for the use of the RTDV as an effective means to increase fertilizer use efficiency in agriculture.

Branching and size of CTAB-coated gold nanostars control the colorimetric detection of bacteria

Rapid detection of pathogenic bacteria is challenging because conventional methods require long incubation times. Nanoparticles have the potential to detect pathogens before they can cause an infection. Gold nanostars have recently been used for colorimetric biosensors but they typically require surface modification with antibodies or aptamers for cellular detection. Here, CTAB-coated gold nanostars have been used to rapidly (<5 min) detect infective doses of a model Gram-positive pathogen Staphylococcus aureus by an instrument-free colorimetric method. Varying the amounts of gold nanoseed precursor and surfactant can tune the size and degree of branching of gold nanostars as studied here by transmission electron microscopy. The size and morphology of gold nanostars determine the degree and rate of color change in the presence of S. aureus. The optimal formulation achieved maximum color contrast in the presence of S. aureus and produced a selective response in comparison to polystyrene microparticles and liposomes. These gold nanostars were characterized using UV-Visible spectroscopy to monitor changes in their surface plasmon resonance peaks. The visual color change was also quantified over time by measuring the RGB components of the pixels in the digital images of gold nanostar solutions. CTAB-coated gold nanostars serve as a promising material for simple and rapid detection of pathogens.

Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentally-induced dry eye syndrome

Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly(d, l-lactide) and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A (CycA) and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute (1 week) and chronic (12 weeks) studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.

Responses of Staphylococcus aureus bacterial cells to nanocrystalline nickel nanostructures.

A broad range of human diseases are associated with bacterial infections, often initiated by specific adhesion of a bacterium to the target environment. Despite the significant role of bacterial adhesion in human infectious diseases, details and mechanisms of bacterial adhesion have remained elusive. Herein, we study the physical interactions between Staphylococcus aureus, a type of micro-organism relevant to infections associated with medical implants, and nanocrystalline (nc) nickel nanostructures with various columnar features, including solid core, hollow, x-shaped and c-shaped pillars. Scanning electron microscopy results show the tendency of these bacterial cells to attach to the nickel nanostructures. Moreover, unique single bacterium attachment characteristics were observed on nickel nanostructures with dimensions comparable to the size of a single bacterium.

Synthesis of curdlan-graft-poly(ethylene glycol) and formulation of doxorubicin-loaded core–shell nanoparticles

A new core–shell nanoparticle containing the chemotherapeutic drug doxorubicin was formulated via amphiphilic graft copolymer self-assembly using curdlan-graft-poly(ethylene glycol) (curdlan-g-PEG). The graft copolymer was synthesized through the dicyclohexylcarbodiimide ester linkage of carboxylated PEG to the hydroxyl groups of the curdlan backbone. The nanoparticles were 109.9 nm in size and encapsulated doxorubicin in high yield (4%–5% wt/wt). The nanoparticles also controlled the release of doxorubicin over 24 h with a release profile that followed a Fickian diffusion model. The biocompatibility of curdlan-g-PEG was confirmed by hemolysis assay. This is the first nanoparticle formulated using the hydrophobicity of curdlan for concealing the immunomodulatory potential of curdlan within the core.

Sliding-strip microfluidic device enables ELISA on paper

This article describes a 3D microfluidic paper-based analytical device that can be used to conduct an enzyme-linked immunosorbent assay (ELISA). The device comprises two parts: a sliding strip (which contains the active sensing area) and a structure surrounding the sliding strip (which holds stored reagents—buffers, antibodies, and enzymatic substrate—and distributes fluid). Running an ELISA involves adding sample (e.g. blood) and water, moving the sliding strip at scheduled times, and analyzing the resulting color in the sensing area visually or using a flatbed scanner. We demonstrate that this device can be used to detect C-reactive protein (CRP)—a biomarker for neonatal sepsis, pelvic inflammatory disease, and inflammatory bowel diseases—at a concentration range of 1–100 ng/mL in 1000-fold diluted blood (1–100 µg/mL in undiluted blood). The accuracy of the device (as characterized by the area under the receiver operator characteristics curve) is 89% and 83% for cut-offs of 10 ng/mL (for neonatal sepsis and pelvic inflammatory disease) and 30 ng/mL (for inflammatory bowel diseases) CRP in 1000-fold diluted blood respectively. In resource-limited settings, the device can be used as a part of a kit (containing the device, a fixed-volume capillary, a pre-filled tube, a syringe, and a dropper); this kit would cost ~

Discrimination of Proteins Using an Array of Surfactant-Stabilized Gold Nanoparticles

0.50 when produced in large scale (>100,000 devices/week). This kit has the technical characteristics to be employed as a pre-screening tool, when combined with other data such as patient history and clinical signs.