Engineered microbubbles decorated with red emitting carbon nanoparticles for efficient delivery and imaging.

Altering the route of uptake by the cells is an attractive strategy to overcome drug-receptor adaptation problems. Carbon nanoparticles (CNPs) with emission beyond tissue autofluorescence for imaging biological tissues were used to study the phenomenon of uptake by the cells. In this regard, red-emitting carbon nanoparticles (CNPs) were synthesized and incorporated onto lipid microbubbles (MBs). The CNPs showed red emissions in the range of 640 nm upon excitation with 480 nm wavelength of light. Atomic force microscopic and confocal microscopic images showed the successful loading of CNPs onto the MB. Carbon nanoparticle loaded microbubbles (CNP-MBs) were treated with NIH 3 T3 cells at different concentrations. Confocal microscopic imaging studies confirm the presence of CNPs inside the treated cells. Cytotoxicity studies revealed that the CNPs showed minimal toxicity towards cells after loading onto MBs. The CNPs are usually taken up by the cells through the clathrin-mediated (CME) pathway, but when loaded onto MBs, the mechanism of uptake of CNPs is altered, and the uptake by the cells was observed even in the presence of inhibitors for the CME pathway. Loading CNPs onto MBs resulted in the uptake of CNPs by the cell through micropinocytosis and sonophoresis in the presence of ultrasound. The in vivo uptake CNP-MBs were performed in Danio rerio (Zebrafish larvae). This study provides insights into altering the uptake pathway through reformulation by loading nanoparticles onto MBs.

ß-Carotene laden antibacterial and antioxidant gelatin/polyglyceryl stearate nano-hydrogel system for burn wound healing application.

Worldwide, burn wounds are severe health issues prone to bacterial infections and challenging to treat with traditional wound dressings. Therefore, a highly desirable biological macromolecules-based wound dressing with good antioxidant, antibacterial, biocompatible, and a large surface area is required. Herein, aim to develop a biological macromolecules-based physically cross-linked gelatin/polyglyceryl stearate/graphene oxide (GPGO) hydrogel to treat burn wounds. Four sets of hydrogels were prepared by varying GO concentrations. FT-IR, FE-SEM, viscosity analysis, mechanical and thermal stability confirmed the successful preparation of hydrogels with desired properties. Further, ß-carotene (0.5 mg/mL) was encapsulated in hydrogels to enhance the antioxidant activity, and a cumulative release as well as kinetics at pH 6.4 and 7.4 was performed. With an increase in GO concentration, hydrogels showed sustained release of ß-carotene. Among all, GPGO-3 ß hydrogel showed the highest antioxidant potency (57.75 %), hemocompatible (<5 %), cytocompatible (viable with NIH 3T3 cells), cell migration, proliferation, and in vitro wound healing. Also, GPGO-3 ß hydrogel showed efficient antibacterial activity (%inhibition of 85.5 % and 80.2 % and zone of 11 mm and 9.8 mm against S. aureus and E. coli). These results demonstrated the ability of GPGO-3 ß hydrogel as a promising candidate for burn wound healing applications.

Geochemical tracing of synoptic scale modern dust transport over the Northeast Arabian Sea during the southwest monsoon.

During the Southwest monsoon (SWM), aeolian dust is mainly supplied via wet deposition over the northeast Arabian Sea (NEAS). To understand their impact on the biogeochemistry of the Arabian Sea, it is important to identify their sources and characteristics. In this context, wet deposit particulate (WDP) samples were collected at a coastal station (Goa; 15.4° N, 73.8° E) in the NEAS during the SWM for three years. These samples were used to characterize and identify mineral dust sources using mineralogical, elemental, and isotopic (Sr and Nd) signatures. The WDP samples were classified as Beginning of Monsoon (BM, June samples), Mid Monsoon (MM, July-August samples) and End of Monsoon (EM, September samples). Clay mineralogical composition indicate high palygorskite content during BM, which subsequently found to decrease in MM, and almost negligible in EM. However, smectite is highest during MM, with moderate presence of palygorskite during this period. The considerable variation in the relative percentages of clay minerals suggests significant temporal variability in dust sources which is further corroborated by the radiogenic isotopic composition. A strong seasonality in the isotopic composition is observed with 87Sr/86Sr ratio being relatively less radiogenic during MM than the BM and highly radiogenic at the EM. Whereas ƐNd values show an opposite trend to 87Sr/86Sr ratios throughout the monsoon, with more radiogenic ƐNd in the MM, and less radiogenic at the EM. End member mixing plot indicate dominant contribution of dust from the Arabian Peninsula (ARB) and Northeast African (NEA) sources during BM and MM, while a shift towards the Thar desert and Southwest Asian (SWA) sources at the EM. Trace elements associated with different sources were quantified and suggest high Fe concentration is associated with NEA dust sources, despite ARB being major supplier of aeolian dust to the Arabian Sea.

Red emitting fluorescent carbon nanoparticles to track spatio-temporal dynamics of endocytic pathways in model neuroblastoma neurons.

One of the biggest challenges limiting the biological applications of fluorescent carbon-based nanoparticles is their capacity to emit in the red region of the spectrum and simultaneously maintaining the smaller size. These two parameters always go in inverse proportion, thus lagging their applications in biological imaging. Endocytic pathways play important roles in regulating major cellular functions such as cellular differentiation. The Spatio-temporal dynamics of endocytic pathways adopted by various ligands (including nanoparticles) over longer durations in cellular differentiation remain unstudied. Here we have used red-emitting fluorescent carbon nanoparticles to study the endocytic pathways in neuronal cells at different stages of differentiation. These small-sized, bright, red-emitting carbon nanoparticles (CNPs) can be internalized by live cells and imaged for extended periods, thus capturing the Spatio-temporal dynamics of endocytic pathways in model SH-SY5Y derived neuroblastoma neurons. We find that these nanoparticles are preferably taken up via clathrin-mediated endocytosis and follow the classical recycling pathways at all the stages of neuronal differentiation. These nanoparticles hold immense potential for their size, composition, surface and fluorescence tunability, thus maximizing their applications in spatio-temporally tracking multiple cellular pathways in cells and tissues simultaneously.

Water stable, red emitting, carbon nanoparticles stimulate 3D cell invasion via clathrin-mediated endocytic uptake.

Bright fluorescent nanoparticles with excitation and emission towards the red end of the spectrum are highly desirable in the field of bioimaging. We present here a new class of organic carbon-based nanoparticles (CNPs) with a robust quantum yield and fluorescence towards the red region of the spectrum. Using organic substrates such as para-phenylenediamine (PPDA) dispersed in diphenyl ether under reflux conditions, we achieved scalable amounts of CNPs with an average size of 27 nm. These CNPs were readily taken up by different mammalian cells, and we show that they prefer clathrin-mediated endocytosis for their cellular entry route. Not only can these CNPs be specifically taken up by cells, but they also stimulate cellular processes such as cell invasion from 3D spheroid models. This new class of CNPs, which have sizes similar to those of proteinaceous ligands, hold immense potential for their surface functionalization. These could be explored as promising bioimaging agents for biomedical imaging and intracellular drug delivery.

Controlled 3D assembly and stimuli responsive behavior of DNA and peptide functionalized gold nanoparticles in solutions.

DNA mediated directed self assembly of gold nanoparticles (AuNPs) has garnered immense interest due to its ability to precisely control supramolecular assemblies. Most experimental works have relied on utilizing the complementary interactions between the DNA strands to drive the self assembly of AuNPs grafted with DNA strands. In the present work, we have leveraged DNA-peptide interactions to tune the self assembly and stimuli responsive behavior of AuNPs grafted with single stranded DNA (ssDNA) and poly-L-lysine (PLL) chains. Our findings show that the electrostatic interactions between the negatively charged ssDNA grafts and positively charged PLL grafts, drive the self assembly of AuNPs of different sizes into 3D nanostructures. The transmission electron micrographs confirm that the smaller AuNPs grafted with PLL chains form a corona around the large AuNPs grafted with ssDNA like the petals around a flowery core to drive aggregation of large AuNPs. When the grafting of ssDNA and PLL on the different sized AuNPs is swapped, aggregates of large AuNPs mediated by the ssDNA grafts on the smaller AuNPs were observed. The presence of excess ssDNA/PLL chains in solutions affected both the morphology and the mechanism of aggregate formation. Coarse-grain molecular dynamics simulations qualitatively match the experimental findings and provided a scientific rationale to the above findings highlighting the role of chain entropy, molecular connectivity, and charge correlations on the self assembly of AuNPs.

Assessment of aeolian dust concentration, elemental composition, and their wet and dry deposition fluxes over the Northeast Arabian Sea.

Atmospheric aerosol over the Arabian Sea is significantly impacted by the long-range transported mineral dust from the surrounding continents. This transported mineral dust is hypothesized and tested during several studies to see the impacts on the surface ocean biogeochemical processes and subsequently to the Carbon cycle. It is, thus important to quantify dust contributions and their fluxes to the Arabian Sea. Here we assess temporal variability of dust concentration, their elemental characteristics as well as quantify their dry and wet deposition fluxes over the North-eastern Arabian Sea. The dust concentrations were found to vary from 59 to 132 µg m-3 which accounts for 50% to 90% of total mass during dusty days. However, its contribution during pre and post dust storms ranges between 6% and 60%. Relatively higher dust dry deposition flux of 28 ± 7 mg m-2 day-1 (range: 20-44) is estimated for dusty days compared to pre and post dusty days (range: 0.4-22 mg m-2 day-1). In contrast to dry deposition fluxes, significantly higher fluxes are estimated from wet deposition, averaging around 240 ± 220 mg m-2 day-1. These values are five times higher than those reported from cruise samples collected over the Arabian Sea. The contribution of dust to aerosol mass is further ascertained using elemental composition, wherein a significant correlation was observed between Fe and Al (r2 = 0.77) for samples collected during the dusty period, highlighting their similar crustal sources. Our estimation of dust flux over this region has implications for the supply of nutrients associated with natural dust to the surface water of the Arabian Sea.Implications: The Arabian Sea, one of the productive oceanic regions among the global oceans, has been identified as a perennial source of atmospheric CO2. This basin is heavily impacted by atmospheric dust deposition/inputs owing to its geographical location being surrounded by arid and semi-arid regions. It has been hypothesized that aeolian dust plays a significant role in modulating surface water biogeochemical processes including primary productivity, in the Arabian Sea. Furthermore, modelling studies have highlighted on the role of dust (containing Fe) in fueling and enhancing primary productivity in the Arabian Sea. However, quantification of dust deposition fluxes (wet and dry) on seasonal time scale is missing in the literature. This paper aims to partially fulfil this research gap by providing a long-term data of wet and dry deposition fluxes over the northeastern Arabian Sea. We have also discussed their seasonal variability and factors affecting this flux. Thus, this study will be valuable contribution to the aeolian research community and have significant implication toward the role of aeolian deposition to the surface water biogeochemical processes in the Arabian Sea.

Stimuli Responsive, Programmable DNA Nanodevices for Biomedical Applications.

Of the multiple areas of applications of DNA nanotechnology, stimuli-responsive nanodevices have emerged as an elite branch of research owing to the advantages of molecular programmability of DNA structures and stimuli-responsiveness of motifs and DNA itself. These classes of devices present multiples areas to explore for basic and applied science using dynamic DNA nanotechnology. Herein, we take the stake in the recent progress of this fast-growing sub-area of DNA nanotechnology. We discuss different stimuli, motifs, scaffolds, and mechanisms of stimuli-responsive behaviours of DNA nanodevices with appropriate examples. Similarly, we present a multitude of biological applications that have been explored using DNA nanodevices, such as biosensing, in vivo pH-mapping, drug delivery, and therapy. We conclude by discussing the challenges and opportunities as well as future prospects of this emerging research area within DNA nanotechnology.

DNA-Functionalized Nanoparticles for Targeted Biosensing and Biological Applications.

Nanoscale systems have increasingly been used in biomedical applications, enhancing the demand for the development of biomolecule-functionalized nanoparticles for targeted applications. Such designer nanosystems hold great prospective to refine disease diagnosis and treatment. To completely investigate their potential for bioapplications, nanoparticles must be biocompatible and targetable toward explicit receptors to guarantee particular detecting, imaging, and medication conveyance in complex organic milieus, for example, living cells, tissues, and organisms. We present recent works that explore enhanced biocompatibility and biorecognition of nanoparticles functionalized with DNA and different DNA entities such as aptamers, DNAzymes, and aptazymes. We sum up the methods utilized in the amalgamation of complex nanostructures, survey the significant types of multifunctional nanoparticles that have been developed in the course of recent years, and give a perceptual vision of the significant field of nanomedicine. The field of DNA-functionalized nanoparticles holds an incredible guarantee in rising biomedical zones, for example, multimodal imaging, theranostics, and picture-guided treatments.