The real-time, colorimetric detection of analytes via aptamer–gold nanoparticle technology has proven to be an important, emerging technique within the medical field. Of global health importance, the ability to detect vector mosquito species, such as the Aedes (Ae.) aegypti mosquito, and transmitted arboviruses, such as Zika virus, is paramount to mosquito control and surveillance efforts. Herein, we describe the detection of Ae. aegypti salivary protein for vector identification and the detection of Zika virus to assess mosquito infection status by aptamer–gold nanoparticle conjugates. Key to optimization of these diagnostics were gold nanoparticle capping agents and aptamer degree of labelling (i.e., the amount of aptamers per gold nanoparticle). In the present study, detection was achieved for as little as 10 ng Ae. aegypti salivary protein and 1.0 × 105 PFU live Zika virus. These aptamer–gold nanoparticle conjugate diagnostics could one day prove to be useful as deployable nano-based biosensors that provide easy-to-read optical read outs through a straightforward red-to-blue colour change either within a diagnostic solution or atop a card/membrane-based biosensor.
25 September 2020 in PLOS Neglected Tropical Diseases
Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag+ controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNP-blood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused ~60% mortality in 3rd instar larvae when larval food was absent, while CNPs yielded only ~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag+ needed to achieve comparable larvicidal activity (4.2 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development. Viral diseases like Zika and dengue fevers that are vectored by mosquitoes cause illness and death in populations worldwide. Chemical pesticides are the frontline tools used to control mosquitoes, however, development of resistance by the vectors to these agents overtime ultimately reduces effectiveness. Hence, the development of new pesticides that do not spur the development of resistance is of paramount importance. We therefore developed and characterized various types of well-defined cerium oxide nanoparticles (nanoceria) and studied the impacts on Aedes (Ae.) aegypti mosquitoes resulting from exposure to these novel agents. We found that nanoceria not only have larvicidal potential, but also alter the life history traits (e.g., reduced egg hatch proportion and altered sex ratio) of the subsequent adult mosquitoes exposed to these nanoparticles during the larval stage. One of the most interesting and important findings of our study is that exposure of female Ae. aegypti mosquitoes to nanoceria via blood meals significantly reduced egg clutches apparently via arresting oocyte growth, thereby interfering with the ultimate development and production of eggs. Thus, this study reveals until-now-unappreciated impacts of nanoceria exposure on Ae. aegypti mosquitoes and helps inform how these kinds of agents can be potentially deploy in control strategies.
Cell-based therapies hold promise for many chronic conditions; however, the continued need for immunosuppression along with challenges in replacing cells to improve durability or retrieving cells for safety are major obstacles. We subcutaneously implanted a device engineered to exploit the innate transcapillary hydrostatic and colloid osmotic pressure generating ultrafiltrate to mimic interstitium. Long-term stable accumulation of ultrafiltrate was achieved in both rodents and nonhuman primates (NHPs) that was chemically similar to serum and achieved capillary blood oxygen concentration. The majority of adult pig islet grafts transplanted in non-immunosuppressed NHPs resulted in xenograft survival >100 days. Stable cytokine levels, normal neutrophil to lymphocyte ratio, and a lack of immune cell infiltration demonstrated successful immunoprotection and averted typical systemic changes related to xenograft transplant, especially inflammation. This approach eliminates the need for immunosuppression and permits percutaneous access for loading, reloading, biopsy, and recovery to de-risk the use of “unlimited” xenogeneic cell sources to realize widespread clinical translation of cell-based therapies.
A rapid thermal desorption-gas chromatography-electron ionization-mass spectrometry (TD-GC-EI-MS) method for airborne transfluthrin detection is studied. Active air sampling of 9 L over 1 h at 23 °C through a Tenax®-loaded tube resulted in efficient capture of airborne transfluthrin. Subsequent thermal desorption was employed to achieve an LOD of 2.6 ppqv (parts per quadrillion by volume). A minimum primary desorption temperature of 300 °C is necessary for optimal recovery of sample from the Tenax® adsorbent. The matrix effects of indoor air lead to an error of 10.9% and 10.5% recovery of sample (10 pg and 100 pg loaded tubes, respectively). The linear range was 74–74,000 ppqv with a correlation coefficient of 0.9981. Active air sampling of a novel passive release device revealed a ∼150 pg/L airborne concentration gradient over 1 m, providing spatial characterization of the device’s performance. This efficient method allows for the remote collection of samples and rapid analysis of airborne transfluthrin from industrial applications, optimization studies of commercial products as well as domestic/household monitoring.
23 November 2018 in International Journal of Polymeric Materials and Polymeric Biomaterials
In this study, capillary alginate gel (Capgel™), a collagen and alginate based self-assembling biomaterial, was used as a cellular scaffold for the treatment of ischemic, full-thickness dermal wounds in mice. Capgel™ was synthesized using copper sulfate to form the initial sol before rinsing and stabilizing the patent capillary structures with carbodiimide chemistry. This crosslinked hydrogel was then injected into ischemic, full-thickness dermal wounds and analyzed via histology after 7 and 10 days to assess wound contracture, granulation bed tissue and vascular structures. Capgel™ showed good resorbability and was well-invested with infiltrating host cells and vascular structures during and after resorption. GRAPHICAL ABSTRACT
Three-dimensional (3D) printing has great potential for creating tissues and organs to meet shortfalls in transplant supply, and biomaterial inks are key components of many such approaches. There is a need for biomaterial inks that facilitate integration, infiltration, and vascularization of targeted 3D-printed structures. This study is therefore focused on creating new biomaterial inks from self-assembled capillary alginate gel (Capgel), which possesses a unique microstructure of uniform tubular channels with tunable diameters and densities. First, extrusions of Capgel through needles (0.1–0.8 mm inner diameter) were investigated. It was found that Capgel ink extrudes as slurries of fractured and entangled particles, each retaining capillary microstructures, and that extruded line widths W and particle sizes A were both functions of needle inner diameter D, specifically power-law relationships of W~D0.42 and A~D1.52, respectively. Next, various structures were successfully 3D-printed with Capgel ink, thus demonstrating that this biomaterial ink is stackable and self-supporting. To increase ink self-adherence, Capgel was coated with poly-L-lysine (PLL) to create a cationic “skin” prior to extrusion. It was hypothesized that, during extrusion of Capgel-PLL, the sheared particles fracture and thereby expose cryptic sites of negatively-charged biomaterial capable of forming new polyelectrolyte bonds with areas of the positively-charged PLL skin on neighboring entangled particles. This novel approach resulted in continuous, self-adherent extrusions that remained intact in solution. Human lung fibroblasts (HLFs) were then cultured on this ink to investigate biocompatibility. HLFs readily colonized Capgel-PLL ink and were strongly oriented by the capillary microstructures. This is the first description of successful 3D-printing with Capgel biomaterial ink as well as the first demonstration of the concept and formulation of a self-adherent Capgel-PLL biomaterial ink.