Magnetic Nanoparticles for Biomedicine - Intracellular Delivery: Fundamentals and Applications - page 367

The modified magnetic nanoparticles should be stable against aggregation in both
a biological medium and a magnetic field.
Several compounds with carboxylic, phosphate and sulfate functional groups are
known to bind to the surface of magnetic particles and stabilize them. Citric acid
can be successfully used to stabilize water-based magnetic fluids (ferrofluids) by
coordinating via one or two of the carboxyl residues; this leaves at least one
carboxylic acid group exposed to the solvent, which should be responsible for making
the surface negatively charged and hydrophilic. Other ferrofluids can be stabilized
by ionic interactions, using e.g., perchloric acid or tetramethylammonium hydroxide
(Berger et al. 1999 ; Laurent et al. 2008 ).
In most cases biocompatible (bio)polymers are used for magnetic particles
stabilization and modification. Ideal natural or synthetic polymeric materials
used for particles stabilization should have several important properties; they
should be biocompatible and for many applications also biodegradable, non-
toxic, non-thrombogenic, non-immunogenic and inexpensive. The “ideal” mag-
netically responsive (bio)polymer biocompatible composite nanoparticles should
have the following typical properties: particles diameter below 100 nm, stability
in blood, no activation of neutrophils, no platelet aggregation, avoidance of the
reticuloendothelial system, noninflamatory behavior, prolonged circulation
time, possible immobilization of appropriate biologically active compounds
(e.g., antibodies) and scalable and cost-effective production (Lockman et al.
2002 ). Dextran, a polysaccharide polymer composed exclusively of a-D-glu-
copyranosyl units with varying degrees of chain length and branching has often
been used as a polymer coating mostly because of its excellent biocompatibility.
The formation of magnetite in the presence of dextran 40,000 was reported for
the first time in 1980s (Molday and Mackenzie 1982 ). The same procedure has
been used for the preparation of approved magnetic resonance contrast agents
Ferumoxtran-10 (Combidex, Sinerem); this material has a small hydrodynamic
diameter (15-30 nm), and shows a prolonged blood residence time, which
allows this USPIO (“Ultrasmall superparamagnetic iron oxides”) to access mac-
rophages located in deep and pathologic tissues (such as lymph nodes, kidney,
brain, osteoarticular tissues, etc.). Other common biopolymer coatings are
formed e.g. by carboxymethylated dextran, carboxydextran, starch, chitosan,
alginate, arabinogalactan or glycosaminoglycan, while polyethylene glycol
(PEG) and polyvinyl alcohol (PVA) represent biocompatible synthetic polymers
(Laurent et al. 2008 ).
Magnetic nanoparticles often form a magnetic part of magnetically responsive
composite microparticles formed from various synthetic polymers, biopolymers,
inorganic materials, microbial cells or plant materials (Safarik and Safarikova
2009b ). Superparamagnetic monodisperse microparticles composed of polystyrene
matrix with entrapped maghemite nanoparticles (approx. 8 nm in diameter; Fonnum
et al. 2005 ), known as Dynabeads (Invitrogen), have been used in enormous amount
of bioapplications, especially in molecular biology, cell biology, microbiology and
protein separation.