Engulfment Of Nanoparticles Research Articles

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Model for particle capture by the solid-liquid interface during solidification of metal matrix nanocomposites

A sharp-interface model for solidification of nanocomposites with nanoparticle-interface interaction is presented. The main novelty of the work is that the engulfment or non-engulfment of nanoparticles is modelled as a function of the local interface velocity and a particle size-based critical velocity. This is incorporated through a variable partitioning coefficient while solving the nanoparticle conservation equation which is modelled similar to an alloying constituent. The movement of nanoparticles is governed by nanoparticle-interface interaction and by diffusion due to Brownian motion. The model couples a sharp-interface solidification model, species transport model and nanoparticle transport model. Thus, the engulfment and the resultant distribution of nanoparticles in the solidified region can be predicted for different combinations of initial undercooling and nanoparticle size. The effect of accumulated nanoparticles on the solute transport and solidification rate is also included in the model. Results show that the engulfment of smaller nanoparticles is very low resulting in high accumulation near the interface. This results in a high restriction to solute diffusion and solidification. Combined variation of initial undercooling and particle size shows that the average engulfment values for initial undercooling of 0.3, 0.5, and 0.7 are 2.75 %, 7.75 % and 21.50 % for r* = 0.1, 15.5 %, 53.5 %, and 82.5 % for r* = 0.5, and 38.0 %, 77.75 %, and 93.25 % for r* = 0.9. Thus, the engulfment of nanoparticles into the solid improves with increase in nanoparticle size and with the increase in solidification rate.

Abstract P-35: Cryo-Electron Tomography of Protein Conjugated Upconverting Nanophosphors

Background: Over the past decades, significant advances have been made in the field of creating nanobioreagents for solving modern medicine problems (Grebenik et al., JBO, 2013). However, the problem of their low accumulation rate in pathological tissue in vivo experiments still remains. First of all, it is associated with the adsorption of blood proteins on the surface of nanobioreagents and the protein layer formation, which significantly changes the surface properties, which leads to their rapid excretion by the reticuloendothelial system. In particular, it is possible to reduce the blood plasma proteins adsorption and increase the time spent in the circulatory system by forming a coating of proteins. Methods: In situ cryоelectron tomography (Cryo-ET) is the only method that allows the experimental observation of protein structures on the nanoparticle’s surface in their natural functional state. The basic principle of the method is to obtain a series of projections of a vitrified sample thin lamella at different tilt angles related to an incident electron beam. Their further processing leads to obtaining the volumetric information about the structure of the sample. The use of a cryo-focused ion beam (Cryo-FIB) in specimen thinning makes it possible to carry out experiments with thin sections of cellular structures and observe the penetration of nanoparticles into the intracellular environment. Results: Upconverting nanophosphors (AN) were used as a nanoplatform for creating a protein coating. To create a protein coating on the AN surface, they were functionalized using an amphiphilic polymer containing carboxyl groups. Then, conjugation with protein molecules from the class of immunoglobulins was carried out by the method of carbodiimide activation. At each stage of synthesis and modification, AN solutions with different size distribution were vitrified for subsequent tomography. After a series of experiments to study the morphology of nanoparticles, an experiment on their successful absorption by cells of the cancer line A549 was carried out. Conclusion: Within this work, a series of in situ Cryo-ET methods were proposed and applied for structural characterization and visualization of the processes of synthesis, modification, and engulfment of nanoparticles into cellular systems. For the first time in its native form, the engulfment of ANF into the internal environment of the A549 cancer line cells was demonstrated.

Engulfment and distribution of second-phase nanoparticle during dendrite solidification of an Al–Si binary alloy: a simulation study

To achieve optimum strengthening effects of external nanoparticles (NPs), uniform dispersion of NPs in the melt is necessary for the casting manufacturing of metal matrix nanocomposites in which dislocation-based strengthening mechanisms play a significant role. However, the engulfment of nanoparticles within the solidifying grains and the avoidance of pushing them outside the solidification front are always a major challenge. Therefore, the understanding of local interface velocity and interface/particle dynamics during alloy solidification is of significant importance. Existing numerical studies on particle engulfment/pushing do not take into consideration the anisotropy of crystal growth and assume planar solidification interface, and thus they are unable to obtain the nanoparticle distribution in realistic alloy solidification. In this research, we investigate the engulfment/push behavior and the overall distribution of SiO2 nanoparticles in the dendrite solidification of an Al–Si binary alloy. Phase-field method is used to simulate the dendrite growth and to predict local solidification front velocity. In combination with the critical engulfment velocity obtained from a non-steady-state particle/front interaction model, the engulfment/push behavior of the entire solidification domain as well as the final distribution of nanoparticles can be analyzed. It is found that the distribution pattern of NPs obtained from simulation is overall consistent with the limited experimental results in the literature. In addition, the two main dislocation-based strengthening effects, e.g., Orowan bowing and CTE (coefficient of thermal expansion) mismatch strengthening, brought by external nanoparticles are quantitatively predicted. The degree of undercooling (60, 80, and 100 K) and nanoparticle size (10, 20, 30, 40, and 50 nm) are varied to investigate their influence on the NP engulfment behavior and the resulted strengthening effects.