Surface molecular orientation of bound ligand, critical

Surface
modification chemistry

Chemical
approaches are categorised as covalent linkages (Direct nanoparticle
conjugation, click chemistry and covalent linker chemistry) and physical interactions
(Electrostatic, hydrophilic/hydrophobic, affinity interactions). Covalent
linkages are strong and stable covalent bonds specifically formed with
functional groups like carboxylic acid, amino and thiol groups on the nanoparticle
surfaces and ligands. E.g. Polymer coatings (Chitosan, dextran) dictated the
type and number of functional group on each nanoparticle or terminal ends (PEG).

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Direct
nanoparticle conjugation: 
Here functional groups are directly bonded to reactive ligands or
linkage reactions and are facilitated by the aid of catalysts. Eg: Amine,
sulphide, aldehyde etc.

Click
Chemistry: Sharpless and co-workers developed a new approach
of direct conjugation known as Click chemistry (Kolb, Finn & Sharpless, 2001). These reactions are
fast, efficient and require mild reaction conditions and create water soluble
biocompatible ligands. E.g. Azide and alkyne reactive groups are highly
specific and unreactive functional groups ensuring specific conjugation at the
desired locations on the reactive moiety (Hein, Liu & Wang, 2008). Disadvantage: Since copper
is most commonly used catalyst in the reaction, the use of Cu or consumptions
may be linked to few disorders like neurological disorder, kidney disorder,
hepatitis etc.

In
linker chemistry, linker molecule offers control over the
molecular orientation of bound ligand, critical when protecting ligand
functionality. Additionally linkers are selectively cleaved for the use of
ligand quantification, controlled release and other applications        (Veiseh, Gunn& Zhang, 2010).

Physical
interactions have unique advantages like rapid speed
of binding, high efficiencies and no need for intermediate modification steps.
Many scientists have worked with magnetic nanoparticles coated with cationic
polymers like PEI, which is then complexed with negatively charged plasmid DNA
molecules (Chorny, Polyak,
Alferiev, Walsh, Friedman & Levy, 2007 ; Park, et al., 2008).). Hydrophobic/hydrophilic
interactions are highly useful for adsorbing hydrophobic drugs on magnetic
nanosystems. Affinity interactions have shown effective for bioconjugation of
targeting ligands to nanosystems. The linkages formed are highly stable and the
strongest of all non covalent linkages. Unlike hydrophobic and electrostatic
interactions, affinity binding is not sensitive to the environment conditions
like change in pH, salinity and hydrophilicity (Gunn, et al., 2008) hence used
in immunotherapy applications.