Mikhail V. Zyuzin

The influence of the size and aspect ratio of anisotropic, porous CaCO3 particles on their uptake by cells

BackgroundRecent reports highlighting the role of particle geometry have suggested that anisotropy can affect the rate and the pathway of particle uptake by cells. Therefore, we investigate the internalization by cells of porous calcium carbonate particles with different shapes and anisotropies.ResultsWe report here on a new method of the synthesis of polyelectrolyte coated calcium carbonate particles whose geometry was controlled by varying the mixing speed and time, pH value of the reaction solution, and ratio of the interacting salts used for particle formation. Uptake of spherical, cuboidal, ellipsoidal (with two different sizes) polyelectrolyte coated calcium carbonate particles was studied in cervical carcinoma cells. Quantitative data were obtained from the analysis of confocal laser scanning microscopy images.ConclusionsOur results indicate that the number of internalized calcium carbonate particles depends on the aspect ratio of the particle, whereby elongated particles (higher aspect ratio) are internalized with a higher frequency than more spherical particles (lower aspect ratio). The total volume of internalized particles scales with the volume of the individual particles, in case equal amount of particles were added per cell.

Influence of Temperature on the Colloidal Stability of Polymer-Coated Gold Nanoparticles in Cell Culture Media.

The temperature-dependence of the hydrodynamic diameter and colloidal stability of gold-polymer core-shell particles with temperature-sensitive (poly(N-isopropylacrylamide)) and temperature-insensitive shells (polyallylaminine hydrochloride/polystyrensulfonate, poly(isobutylene-alt-maleic anhydride)-graft-dodecyl) are investigated in various aqueous media. The data demonstrate that for all nanoparticle agglomeration, i.e., increase in effective nanoparticle size, the presence of salts or proteins in the dispersion media has to be taken into account. Poly(N-isopropylacrylamide) coated nanoparticles show a reversible temperature-dependent increase in size above the volume phase transition of the polymer shell when they are dispersed in phosphate buffered saline or in media containing protein. In contrast, the nanoparticles coated with temperature-insensitive polymers show a time-dependent increase in size in phosphate buffered saline or in medium containing protein. This is due to time-dependent agglomeration, which is particularly strong in phosphate buffered saline, and induces a time-dependent, irreversible increase in the hydrodynamic diameter of the nanoparticles. This demonstrates that one has to distinguish between temperature- and time-induced agglomerations. Since the size of nanoparticles regulates their uptake by cells, temperature-dependent uptake of thermosensitive and non-thermosensitive nanoparticles by cells lines is compared. No temperature-specific difference between both types of nanoparticles could be observed.

Synthesis and functionalization of monodisperse near-ultraviolet and visible excitable multifunctional Eu3+, Bi3+:REVO4 nanophosphors for bioimaging and biosensing applications

Near-ultraviolet and visible excitable Eu- and Bi-doped NPs based on rare earth vanadates (REVO4, RE = Y, Gd) can be used for bioimaging and biosensing applications.

Luminescent Rare-earth-based Nanoparticles: A Summarized Overview of their Synthesis, Functionalization, and Applications

Rare-earth-based nanoparticles are currently attracting wide research interest in material science, physics, chemistry, medicine, and biology due to their optical properties, their stability, and novel applications. We present in this review a summarized overview of the general and recent developments in their synthesis and functionalization. Their luminescent properties are also discussed, including the latest advances in the enhancement of their emission luminescence. Some of their more relevant and novel biomedical, analytical, and optoelectronic applications are also commented on.

Rare earth based nanostructured materials: synthesis, functionalization, properties and bioimaging and biosensing applications

Abstract Rare earth based nanostructures constitute a type of functional materials widely used and studied in the recent literature. The purpose of this review is to provide a general and comprehensive overview of the current state of the art, with special focus on the commonly employed synthesis methods and functionalization strategies of rare earth based nanoparticles and on their different bioimaging and biosensing applications. The luminescent (including downconversion, upconversion and permanent luminescence) and magnetic properties of rare earth based nanoparticles, as well as their ability to absorb X-rays, will also be explained and connected with their luminescent, magnetic resonance and X-ray computed tomography bioimaging applications, respectively. This review is not only restricted to nanoparticles, and recent advances reported for in other nanostructures containing rare earths, such as metal organic frameworks and lanthanide complexes conjugated with biological structures, will also be commented on.

Quantitative uptake of colloidal particles by cell cultures.

The use of nanotechnologies involving nano- and microparticles has increased tremendously in the recent past. There are various beneficial characteristics that make particles attractive for a wide range of technologies. However, colloidal particles on the other hand can potentially be harmful for humans and environment. Today, complete understanding of the interaction of colloidal particles with biological systems still remains a challenge. Indeed, their uptake, effects, and final cell cycle including their life span fate and degradation in biological systems are not fully understood. This is mainly due to the complexity of multiple parameters which need to be taken in consideration to perform the nanosafety research. Therefore, we will provide an overview of the common denominators and ideas to achieve universal metrics to assess their safety. The review discusses aspects including how biological media could change the physicochemical properties of colloids, how colloids are endocytosed by cells, how to distinguish between internalized versus membrane-attached colloids, possible correlation of cellular uptake of colloids with their physicochemical properties, and how the colloidal stability of colloids may vary upon cell internalization. In conclusion three main statements are given. First, in typically exposure scenarios only part of the colloids associated with cells are internalized while a significant part remain outside cells attached to their membrane. For quantitative uptake studies false positive counts in the form of only adherent but not internalized colloids have to be avoided. pH sensitive fluorophores attached to the colloids, which can discriminate between acidic endosomal/lysosomal and neutral extracellular environment around colloids offer a possible solution. Second, the metrics selected for uptake studies is of utmost importance. Counting the internalized colloids by number or by volume may lead to significantly different results. Third, colloids may change their physicochemical properties along their life cycle, and appropriate characterization is required during the different stages.

Comprehensive and Systematic Analysis of the Immunocompatibility of Polyelectrolyte Capsules

The immunocompability of polyelectrolyte capsules synthesized by layer-by-layer deposition has been investigated. Capsules of different architecture and composed of either non-degradable or biodegradable polymers, with either positively or negatively charged outer surface, and with micrometer size, have been used, and the capsule uptake by different cell lines has been studied and quantified. Immunocompatibility studies were performed with peripheral blood mononuclear cells (PBMCs). Data demonstrate that incubation with capsules, at concentrations relevant for practical applications, did not result in a reduced viability of cells, as it did not show an increased apoptosis. Presence of capsules also did not result in an increased expression of TNF-α, as detected with antibody staining, as well as at mRNA level. It also did not result in increased expression of IL-6, as detected at mRNA level. These results indicate that the polyelectrolyte capsules used in this study are immunocompatible.

Role of the Protein Corona Derived from Human Plasma in Cellular Interactions between Nanoporous Human Serum Albumin Particles and Endothelial Cells

The presence of a protein corona on various synthetic nanomaterials has been shown to strongly influence how they interact with cells. However, it is unclear if the protein corona also exists on protein particles, and if so, its role in particle-cell interactions. In this study, pure human serum albumin (HSA) particles were fabricated via mesoporous silica particle templating. Our data reveal that various serum proteins adsorbed on the particles, when exposed to human blood plasma, forming a corona. In human umbilical vein endothelial cells (HUVECs), the corona was shown to decrease particle binding to the cell membrane, increase the residence time of particles in early endosomes, and reduce the amount of internalized particles within the first hours of exposure to particles. These findings reveal important information regarding the mechanisms used by vascular endothelial cells to internalize protein-based particulate materials exposed to blood plasma. The ability to control the cellular recognition of these organic particles is expected to aid the advancement of HSA-based materials for intravenous drug delivery.

Catalysis by multifunctional polyelectrolyte capsules

Gold nanoparticles and nanocomposites have high catalytic performance for several chemical reactions. Here we present gold and iron oxide nanoparticle modified polymer capsules as porous and multifunctional platforms for catalysis. Layer-by-layer polyelectrolyte microcapsules were formed on calcium carbonate template cores loaded with gold nanoparticles, allowing for high gold loading of the capsules. Magnetic nanoparticles were incorporated in the polymeric shells of the capsules, allowing for magnetic separation. The influence on the catalytic behaviour of gold was studied in terms of the nanoparticle size, the presence of a polymeric shell, and the presence of the magnetic nanoparticles in the shell, by using the model electron transfer reaction between hexacyanoferrate(III) and borohydride.

Luminescent rare earth vanadate nanoparticles doped with Eu3+ and Bi3 for sensing and imaging applications

Nanoparticles (NPs) are attracting interest in nanomedicine due to their potential medical applications, ranging from optical biolabels and contrast agents for magnetic resonance imaging to carriers for drug and gene delivery for disease therapy.[1] Rare earth (RE) based nanophosphors exhibit important advantages compared with other available luminescent materials, such as quantum dots and nanostructures functionalized with organic dyes, due to their lower toxicities, photostabilities, high thermal and chemical stabilities, high luminescence quantum yields, and sharp emission bands.[2] Yttrium orthovanadate NPs doped with Eu3+ and Bi3+, functionalized with poly acryl acid (PAA), and excitable by near-ultraviolet light have been synthesized by homogeneous precipitation at 120 °C from solutions of rare earth precursors (yttrium acetylacetonate and europium nitrate), bismuth nitrate, sodium orthovanadate, and PAA, in an ethylene glycol/water mixture. Quasispheres with sizes from 93 to 51 nm were obtained. The as synthesized NPs were already functionalized with PAA. The NPs showed the typical red luminescence of Eu3+, which can be excited with near-UV light through an energy transfer from the vanadate anion. The presence of Bi3+ shifts the maximum of the broad excitation band from 280 nm to 342 nm. This excitation path is much more efficient than the direct excitation of the Eu3+ electronic levels, and results in a much higher luminescence. The NPs can be uptaken by HeLa cells, and are eventually located in the lysosomes after being internalized. Finally, the functionalization with PAA provides -COOH anchors for adding functional ligands of biomedical interest that can be used for sensing applications.