Nanoparticles need to be surface modified if they are not water soluble, monodisperse, or biocompatible. Most of the biological reactions are carried out in an aqueous environment. However, some nanoparticles such as QDs are synthesized in organic solvents and are insoluble in water. Furthermore, nanoparticles have a large surface area-volume-ratio and tend to agglomerate to reduce their surface energy. When nanoparticles agglomerate, or adsorb plasma proteins, they are quickly eliminated from the blood stream by macrophages of the mononuclear phagocyte system (MPS) before they can reach target tissues , causing biocompatibility problems. One of the effective approaches to solving these problems is to modify
the surfaces of nanoparticles with some coatings of desirable functionality, and thus change the intrinsic physicochemical properties of nanoparticles. Coating nanoparticles with self-assembled monolayers of surfactant molecules has demonstrated prevention of the agglomeration and improvement of the biocompatibility . Here we use QDs as an example to show how to do surface modification on QDs.
One method involves the surface exchange of hydrophobic surfactant molecules for polar species. It has also shown that the TOPO ligands on the QD surface may be replaced with heterobifunctional linker molecules, which provides both hy-drophilic character and functional groups for further bioconjugation [6,42]. This method was initially shown to work well for linker molecules such as mercap-toacetic acid, mercaptosuccinic acid, glutathione, dithiothreitol, and histidine. Later, it was found that it could be applicable to a wide range of bifunctional compounds containing sulf-hydryl groups [43-45]. However, QDs capped with small bifunctional linker molecules are easily degraded by hydrolysis or oxidation of the capping ligand . To overcome this problem, a more laborious but more stable method was developed [5,47]. The first step in the surface silanization is to replace the surfactant TOPO by thiol-containing silane monomers to form an initial silica shell (Figure 14.3). Subsequently, phosphonate-, polyethyleneglycol-, or ammonium-containing silane monomers, along with the thiol-containing monomer can be added to increase the thickness of the silica shell. This allows the QDs to
have a hydrophilic surface and functional groups on the surface for conjugation with biomolecules [47,48].
Another method involves phase transfer using amphiphilic molecules that behave as detergents for solubilizing the QDs coated with hydrophobic groups. This method is especially advantageous as it allows for the retention of the original surfactant molecules, which seem to increase the stability and fluorescence efficiency of the QDs over those where the original surface has been completely changed or exchanged with a heterobifunctional linker molecule . The original TOPO ligands on the QD surface are used to interact with an amphiphilic polymer such as octylamine-modified polyacrylic acid and finally lead to the formation of a stable hydrophilic shell around the QD . Another example is to encapsulate TOPO-coated QDs with phospholipid molecules. The hydrocarbon tails of the phospho-lipids are interlocked with the alkyl chains on the QD surfaces, and the polar phosphate head groups are self-assembled to form micelles in the solution .
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