Nanoparticles and Taylor dispersion as a linear time-invariant system

The physical principles underpinning Taylor dispersion offer a high dynamic range to characterize the hydrodynamic radius of particles. While Taylor dispersion grants the ability to measure radius within nearly 5 orders of magnitude, the detection of particles is never instantaneous. It requires a finite sample volume, a finite detector area, and a finite detection time for measuring absorbance. First we show that these practical requirements bias the analysis when the self-diffusion coefficient of particles is high, which is typically the case of small nanoparticles. Second we show that the accuracy of the technique may be recovered by treating Taylor dispersion as a linear time- invariant system, which we prove by analyzing the Taylor dispersion spectra of two iron-oxide nanoparticles measured under identical experimental conditions. The consequence is that such treatment may be necessary whenever Taylor dispersion analysis is not optimized for a given size but dedicated to characterize broad groups of particles of varying size and material

Heating behavior of magnetic iron oxide nanoparticles at clinically relevant concentration

Magnetic hyperthermia for cancer treatment has gained significant attention in recent years, due to its biocompatibility of applied nanoparticles and the possibility for spatially localized heating in deep tissues. Clinical treatments use nanoparticle concentrations of 112 mg Fe/mL, while the concentrations experimental studies have addressed are considerably smaller, usually between 0.1 and 30 mg/mL. Therefore, it is not clear whether such experiments correspond to the magnetic properties found in clinical applications. In this regard, we studied the thermal behavior of superparamagnetic iron oxide nanoparticles (SPION) with the most common particle shapes used in the field, including spherical (core diameters 11 and 19 nm), cubic (15 nm) and ellipsoidal (23 nm with an aspect ratio of 1.45), at concentrations ranging from 5 to 80 mg Fe/mL. Their shape, size, crystallinity, magnetic, and thermal behavior were characterized via transmission electron microscopy, dynamic light scattering, Taylor dispersion analysis, X-ray diffraction, alternating gradient magnetometry, and lock-in thermography. Spherical and cubic nanoparticles displayed linear heating slopes, independent from size, shape and concentration, resulting in unchanged specific absorption rates (SAR). Ellipsoids showed the same behavior until 50 mg/mL, above which a decreasing heating slope trend was found, without evidence as to what causes this behavior. However, the presented results highlight the importance of colloidally stable SPIONs in magnetic hyperthermia to obtain maximum heating power by minimum particle dosage

Artificial lysosomal platform to study nanoparticle long-term stability

Nanoparticles (NPs) possess unique properties useful for designing specific functionalities for biomedi- cal applications. A prerequisite of a safe-by-design and effective use in any biomedical application is to study NP–cell interactions to gain a better understanding of cellular consequences upon exposure. Cellular uptake of NPs results mainly in the localization of NPs in the complex environment of lysosomes, a compartment which can be mimicked by artificial lysosomal fluid. In this work we showed the applicability of lysosomal fluid as a platform for a fast assessment of gold, iron oxide and silica NP stability over 24 h in a relevant biological fluid, by using multiple analytical methods

Lock-in thermography as a rapid and reproducible thermal characterization method for magnetic nanoparticles

Lock-in thermography (LIT) is a sensitive imaging technique generally used in engineering and materials science (e.g. detecting defects in composite materials). However, it has recently been expanded for investigating the heating power of nanomaterials, such as superparamagnetic iron oxide nanoparticles (SPIONs). Here we implement LIT as a rapid and reproducible method that can evaluate the heating potential of various sizes of SPIONs under an alternating magnetic field (AMF), as well as the limits of detection for each particle size. SPIONs were synthesized via thermal decomposition and stabilized in water via a ligand transfer process. Thermographic measurements of SPIONs were made by stimulating particles of varying sizes and increasing concentrations under an AMF. Furthermore, a commercially available SPION sample was included as an external reference. While the size dependent heating efficiency of SPIONs has been previously described, our objective was to probe the sensitivity limits of LIT. For certain size regimes it was possible to detect signals at concentrations as low as 0.1 mg Fe/mL. Measuring at different concentrations enabled a linear regression analysis and extrapolation of the limit of detection for different size nanoparticles

Gut microbiome and circulating bacterial DNA ("blood microbiome") in a mouse model of total parenteral nutrition: Evidence of two distinct separate microbiotic compartments

Background & aims: Total parenteral nutrition (TPN) causes gut atrophy, dysbiosis and leakage of the gut barrier. This study aimed to characterize the gut microbiome in response to different TPNs and tested the hypothesis whether increased gut permeability in TPN would lead to changes in the circulating bacterial DNA ("blood microbiome"). Methods: Male C57BL/6J mice were randomly allocated to the following groups for seven days (1) chow-fed control (C) without jugular vein catheter (JVC, n=6) (2) chow-fed with JVC and infusion of saline (S) (n = 6) (3) Intralipid-based TPN (n-6:n-3 ratio 7:1) (IL, n = 6) (4) Omegaven-based TPN (n-6:n-3 ratio 1:8) (OV, n = 6). Blood was collected by cardiac puncture and feces (stool pellet) were collected from the colon. Blood and stool samples were analyzed by 16S rRNA gene sequencing. Results: TPN administration was associated with a compositional shift in the gut microbial community that involved the expansion of Bacteroidota along with a decrease in gut bacteria belonging to the Firmicutes phylum as compared to chow-fed mice. Gram-negative Verrucomicrobiota and Proteobacteria were also increased in the gut microbiome of mice receiving TPN. Gammaproteobacteria, namely Burkholderiales, were specifically increased in Intralipid-based TPN. On the other hand, Proteobacteria and Actinobacteriota were the dominant taxa in blood samples. The families Comamonadaceae and Burkholderiaceae (both from Burkholderiales order) were increased in the "blood microbiome" of mice with indwelling JVC when compared with chow-fed mice without JVC. The increase in Burkholderiaceae was more pronounced in Intralipid-based TPN. Conclusions: Profound changes in the gut microbiome of mice subjected to TPN occurred, which were not reflected in the "blood microbiome" suggesting that the gut and "blood microbiome" represent two rather distinct separate microbiotic compartments. The parenteral provision of n-3 fatty acids appears to protect against proinflammatory bacteria in the gut and against the increased presence of JVC-associated bacteria as measured by circulating bacterial DNA. Keywords: Blood; Dysbiosis; Gut; Microbiome; Total parenteral nutritio

Gut microbiome and circulating bacterial DNA (“blood microbiome”) in a mouse model of total parenteral nutrition: Evidence of two distinct separate microbiotic compartments

Background & aims: Total parenteral nutrition (TPN) causes gut atrophy, dysbiosis and leakage of the gut barrier. This study aimed to characterize the gut microbiome in response to different TPNs and tested the hypothesis whether increased gut permeability in TPN would lead to changes in the circulating bacterial DNA (“blood microbiome”). Methods: Male C57BL/6J mice were randomly allocated to the following groups for seven days (1) chow-fed control (C) without jugular vein catheter (JVC, n=6) (2) chow-fed with JVC and infusion of saline (S) (n = 6) (3) Intralipid-based TPN (n-6:n-3 ratio 7:1) (IL, n = 6) (4) Omegaven-based TPN (n-6:n-3 ratio 1:8) (OV, n = 6). Blood was collected by cardiac puncture and feces (stool pellet) were collected from the colon. Blood and stool samples were analyzed by 16S rRNA gene sequencing. Results: TPN administration was associated with a compositional shift in the gut microbial community that involved the expansion of Bacteroidota along with a decrease in gut bacteria belonging to the Firmicutes phylum as compared to chow-fed mice. Gram-negative Verrucomicrobiota and Proteobacteria were also increased in the gut microbiome of mice receiving TPN. Gammaproteobacteria, namely Burkholderiales, were specifically increased in Intralipid-based TPN. On the other hand, Proteobacteria and Actinobacteriota were the dominant taxa in blood samples. The families Comamonadaceae and Burkholderiaceae (both from Burkholderiales order) were increased in the “blood microbiome” of mice with indwelling JVC when compared with chow-fed mice without JVC. The increase in Burkholderiaceae was more pronounced in Intralipid-based TPN. Conclusions: Profound changes in the gut microbiome of mice subjected to TPN occurred, which were not reflected in the “blood microbiome” suggesting that the gut and “blood microbiome” represent two rather distinct separate microbiotic compartments. The parenteral provision of n-3 fatty acids appears to protect against proinflammatory bacteria in the gut and against the increased presence of JVC-associated bacteria as measured by circulating bacterial DNA.ISSN:2405-457

Preparation of metallosupramolecular single-chain polymeric nanoparticles and their characterization by Taylor dispersion

Intramolecular cross-linking of polymers can furnish single-chain polymeric nanoparticles (SCPNs), and the use of reversible non-covalent bonds for cross-linking can potentially provide such nanoparticles with stimuli-responsive properties. Here, we report the synthesis of acrylic polymers that carry pendant 2,6-bis(1′-methyl- benzimidazolyl)pyridine ligands, and use these for the preparation of SCPNs through the complex formation with different types of metal ions. The addition of the polymer to solutions containing Fe2+, Zn2+, or Eu3+ ions at low concentrations reliably furnishes the metal–ligand complexes. In order to demonstrate the formation of single-chain polymeric nanoparticles, conventional characterization techniques were complemented by Taylor dispersion analysis, which proved to be particularly useful to accurately measure the hydrodynamic radii of the dispersed particles, in spite of the formation of a small fraction of larger aggregates

Simple and fast evaluation of relaxation parameters of magnetic nanoparticles

The efficacy of magnetic hyperthermia treatment depends on the optimal available magnetic nanoparticles (MNPs) that are excited in a given alternating magnetic field and viscosity of the region of interest. In this regard, assessing the relevant relaxation parameters is of upmost importance and could improve the speed of development of efficient applications. Here, we demonstrate how to deduce all relevant magnetic parameters from fast, independent, and simple experimental measurements such as dynamic light scattering, vibrating sample magnetometer, and lock-in thermography. We study the thermal behaviour of two MNPs with different forms, i.e. spherical and cubical, synthesized in-house by thermal decomposition and coated with 4 different surface agents. By determination of specific absorption rate (SAR) values, hydrodynamic diameters and M−H curves it is possible to compute the magnetic particle volume, dominant relaxation time and magnetocrystalline anisotropy constant. The calculated SAR values derived from these parameters, show good agreement with the experimental determined SAR data, demonstrating the applicability of the reported procedure. Additionally, our results indicate that surface coatings can have minor impacts on the thermal dissipation of Néel relaxation dominated MNPs

Cellulose Nanocrystals with Tethered Polymer Chains: Chemically Patchy versus Uniform Decoration

The site-specific surface modification of colloidal substrates, yielding "patchy" nanoparticles, is a rapidly expanding area of research as a result of the new complex structural hierarchies that are becoming accessible to chemists and materials scientists through colloidal self-assembly. The inherent directionality of cellulose chains, which feature a nonreducing and a reducing end, within individual cellulose nanocrystals (CNCs) renders them an interesting experimental platform for the synthesis of asymmetric nanorods with end-tethered polymer chains. Here, we present water-tolerant reaction pathways toward patchy and uniformly modified CNC hybrids based on atom transfer radical polymerization (ATRP) and initiators that were linked to the CNCs with carbodiimide-mediated coupling and Fischer esterification, respectively. Various monomers, including N-isopropylacrylamide (NIPAM), [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC), and sodium 4-vinylbenzenesulfonate (4-SS), were polymerized from both types of initiator-modified CNCs, yielding chemically patchy and uniform CNC hybrids, via surface-initiated ATRP (SI-ATRP). Interestingly, the stereochemistry of tethered PNIPAM was affected by the precise location of ATRP initiating sites, as evidenced by H-1 NMR and circular dichroism (CD) spectroscopy. This effect may be related to the inherent right-handed chirality of CNCs. CNC/PMETAC hybrids were labeled with gold nanoparticles (AuNPs) in order to visualize the precise location of polymer tethers via cryo-electron microscopy. In some instances, the AuNPs were indeed concentrated at the end groups of the patchy CNC hybrids