Jatuporn Salaklang

Protein Corona Composition of Superparamagnetic Iron Oxide Nanoparticles with Various Physico-Chemical Properties and Coatings

Because of their biocompatibility and unique magnetic properties, superparamagnetic iron oxide nanoparticles NPs (SPIONs) are recognized as some of the most prominent agents for theranostic applications. Thus, understanding the interaction of SPIONs with biological systems is important for their safe design and efficient applications. In this study, SPIONs were coated with 2 different polymers: polyvinyl alcohol polymer (PVA) and dextran. The obtained NPs with different surface charges (positive, neutral, and negative) were used as a model study of the effect of surface charges and surface polymer materials on protein adsorption using a magnetic separator. We found that the PVA-coated SPIONs with negative and neutral surface charge adsorbed more serum proteins than the dextran-coated SPIONs, which resulted in higher blood circulation time for PVA-coated NPs than the dextran-coated ones. Highly abundant proteins such as serum albumin, serotransferrin, prothrombin, alpha-fetoprotein, and kininogen-1 were commonly found on both PVA- and dextran-coated SPIONs. By increasing the ionic strength, soft- and hard-corona proteins were observed on 3 types of PVA-SPIONs. However, the tightly bound proteins were observed only on negatively charged PVA-coated SPIONs after the strong protein elution.

Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells

Abstract Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4+ T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4+ T cells, and induce cytokines. The decreased antigen processing and CD4+ T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.

Superparamagnetic Nanoparticles as a Powerful Systems Biology Characterization Tool in the Physiological Context

Recently, functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have been utilized for protein separation and therapeutic delivery of DNA and drugs. The development of new methods and tools for the targeting and identification of specific biomolecular interactions within living systems is of great interest in the fields of systems biology, target and drug identification, drug delivery, and diagnostics. Magnetic separation of organelles and proteins from complex whole-cell lysates allows enrichment and elucidation of intracellular interaction partners for a specific immobilized protein or peptide on the surface of SPIONs.

Influence of Serum Supplemented Cell Culture Medium on Colloidal Stability of Polymer Coated Iron Oxide and Polystyrene Nanoparticles With Impact on Cell Interactions In Vitro

When nanoparticles interact with cells, the possible cellular responses to the particles depend on an array of parameters, in both particle and biological aspects. On the one hand, the physicochemical properties of the particles (e.g., material, size, shape, and surface charge) are known to play a key role in particle-cell interactions. On the other hand, it has been shown that prior to coming into contact with cells, nanoparticle interaction with the surrounding biological fluid may lead to a change of the initial particle properties. For example, the colloidal behavior of nanoparticles is strongly influenced by the density and viscosity of the surrounding media in both in vitro and in vivo systems. In this study, we demonstrate how the surface charge and composition of different nanoparticles can impact upon their physicochemical characteristics, such as their colloidal stability, within a representative biological fluid and how the change of these parameters can significantly influence the subsequent cellular interaction in vitro. Therefore, we compared charged polymer coated superparamagnetic iron oxide nanoparticles to polystyrene nanoparticles of different surface charges. Particles of lower colloidal stability, namely positively charged superparamagnetic iron oxide nanoparticles, and the polystyrene nanoparticles, showed a higher cell-penetration in vitro than the colloidally stable particles.

Improved dynamic response assessment for intra‐articular injected iron oxide nanoparticles

The emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear/nonproportional intensity to concentration profile due to the competing effects of T1 and T2 relaxation. A concentration calibration phantom and an in vivo study of intra‐articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference‐ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations. Magn Reson Med, 2012.

MULTIFUNCTIONALIZED SPIONs FOR NUCLEAR TARGETING: CELL UPTAKE AND GENE EXPRESSION

Superparamagnetic iron oxide nanoparticles (SPIONs) are used in many biological applications, which necessitate intracellular targeting. Here, we investigate intracellular localization and gene expression in HeLa cells after treatment with functionalized SPIONs. Functional groups investigated included positive amino propyl silane (APS), polyethylene glycol and targeting peptides: nuclear targeting peptide (NTP) and/or cancer cell uptake promoting peptide (cRGD). Results revealed that the intracellular localization of SPIONs was strongly dependent on the surface chemistry. Nuclear targeted SPIONs functionalized with only NTP or both NTP and cRGD were mostly localized in perinuclear endosomes with a small fraction entering the nucleus. The biocompatibility of cells after treatment was also dependent on surface chemistry, where SPIONs functionalized with both NTP and cRGD exhibited a more significant reduction of cell proliferation compared to NTP or cRGD individually. Interestingly, gene expression after treatment with SPIONs was similar, regardless of the surface functionalization or intracellular localization. The results of this study showed that cellular uptake and intracellular localization predominantly depended on the surface chemistry, while gene expression exhibited a more generic response to SPION treatment.

Elegant Synthesis Strategies Using a New Magnetic Bed Reactor: Monoclonal Mouse anti‐CD11b Derivatized Superparamagnetic Iron Oxide Nanoparticles

The new magnetic reactor based solid phase synthesis strategy allows magnetic immobilization of nanoparticles in order to perform the derivatization step(s) with relevant biomolecules on the immobilized magnetic nanoparticles. Monoclonal Mouse anti‐Human CD11b shows affinity toward monocyte/macrophage integrin MAC‐1 (CD11b/CD18) which is involved in leukocyte adhesion and functions as a cell receptor and was coupled on superparamagnetic iron oxide nanoparticles (SPIONs) in this reactor. The resulting anti‐CD11b derivatized SPIONs were analyzed and compared to conventionally derivatized SPIONs. The reactor‐derivatized anti‐CD11b‐SPIONs show enhanced colloidal stability during and after the surface derivatization steps. The yield and quality of the resulting particles can also be significantly improved in terms of reaction time and yield, particle size distribution, and scalability by using this magnetic reactor. These highly specific particles were successfully used in imaging studies of monocytes.