New types of silica-fortified magnetic nanoparticles as tools for molecular biology applications

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Abstract

The synthesis and physico-chemical characterization of superparamagnetic polysaccharide nanoparticles (200–400 nm) with an iron oxide content of 75–80% are described. The robustness of the particle matrix was increased by intercalation of nanoscaled silica. Electrokinetic and streaming potential measurements have been carried out to optimize the silica content of the particles. Specific surface modifications for various in vitro particle applications can also be optimized using these measurements.

Introduction

Biocompatible superparamagnetic nanoparticles comprising iron oxide and a polysaccharide matrix are widely used for in vivo applications including magnetic resonance imaging contrast enhancement [1], [2], [3], [4], [5], tissue specific release of therapeutic agents [6], [7], hyperthermia [8], [9], and magnetic field assisted radionuclide therapy [10]. The in vitro applications of such nanoparticles are still limited to a few special separation processes like the well-established magnetic cell separation [11] carried out with a high-gradient magnetic separation device [12].

Superparamagnetic polysaccharide nanoparticles with a size range below 300 nm have some advantages over synthetic magnetic microparticles for applications in biomedicine, diagnostics and molecular biology. They are biocompatible and non-toxic, have higher effective surface areas and lower sedimentation rates. The hydrophilic surface of the polysaccharide particles decreases nonspecific adsorption processes for proteins or antibodies. But up to now the size-dependent lower attractability of small superparamagnetic nanoparticles to a permanent magnet and the sensitivity of the soft polysaccharide matrix against mechanical stress (centrifugation, peristaltic pump processes, etc.) have prevented further in vitro applications. The commonly used methods to influence the mechanical properties of polysaccharide particles are crosslinking techniques [13] or temperature shock methods [14]. In both cases, the natural structure of the biopolymers is changed and the number of functional groups for further surface modifications is decreased.

Our aim was therefore to develop superparamagnetic polysaccharide particles with a high percentage of iron oxide, consequently nanoparticles with similar magnetic properties as other synthetic magnetic microparticles. Furthermore, we aimed to increase the robustness of the polysaccharide particles by fortification of the particle structure using intercalation of nano-scaled silica without significant changes to the chemical structure of the polysaccharide matrix.

Here we report on the synthesis and physico-chemical characterization of nanomag® particles which are designed for special applications in molecular biology.

Section snippets

Synthesis and physico-chemical characterization of nanomag®

Superparamagnetic polysaccharide particles, nanomag®, were prepared by coating primary aggregates of iron oxide with polysaccharides like dextran, starch or chitosan [10]. The iron oxide aggregates with a size of about 200±50 nm (Fig. 1) were obtained by alkaline precipitation of ferric and ferrous sulfate, followed by gentle washing procedures to decrease the pH value of the iron oxide suspension to pH=7. Corresponding nanoparticles with a silica fortified dextran matrix were synthesized by

Silica-fortified dextran particles

An increasing percentage of nanoscaled silica intercalated in the dextran matrix of the superparamagnetic particles not only leads to an increasing particle diameter but also to changes of the electrophoretic mobility of the particles. Fig. 6 shows the electrophoretic mobility of unmodified dextran nanomag® particles in comparison to the corresponding silica-modified particles as a function of the pH-value. The intercalation of silica leads to a significant increase of the electrophoretic

Applications of nanomag® particles in molecular biology

Dextran and silica-fortified dextran nanoparticles with specific surface designs have been tested in comparison to commercially available synthetic magnetic beads in the fields of automatic DNA purification, protein detection, separation and purification, in test kits for the detection of retroviruses in biological material, in apheresis techniques, in the endotoxin removal, and in magnetic cell separation.

For example at standard automatic DNA purification processes an unspecific DNA binding

Acknowledgements

We would like to thank Thomas Rheinländer (Institute for Diagnostic Research, `Freie Universität Berlin', Germany) for the determination of magnetization, relaxivities, density and iron content of nanomag® particles.

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