Derivitization

Because of their chemical and physical characteristics, nanoparticles exhibit inherent cellular targeting and uptake characteristics. Size and surface charge seem to be the two prominent characteristics that affect inherent nanoparticle targeting and cellular uptake. Because inherent targeting mechanisms may not provide the targeting or delivery characteristics desired, methods to modify nanoparticles with targeting agents can be critical. Although some nanoparticle materials are composed of materials with functional groups useful for chemical coupling, others are not. Such nanoparticle systems must be either modified to allow chemical coupling or doped with reagents that can be used for this modification. A number of coupling strategies have also been worked out that allow for efficient functionalization of nanomaterials through both reversible and irreversible chemistries.14,32 These modifications allow for the coupling of antibodies, receptor ligands, and other potential targeting agents. Similar to the concerns associated with composition of the nanoparticle itself, any modification through chemical derivitization must also be considered with regard to generating materials with unacceptable toxicity or neutralization of the function of the nano-particle or its targeting element.

Nanoparticles have the advantage that they can be modified with multiple ligands to enhance their targeting selectivity and/or allow for simultaneous delivery of diagnostic and therapeutic agents.33 It is important to appreciate the relative size of components used to construct and deri-vitize nanoparticles. For example, a quantum dot may be only 10 nm in diameter. Targeting that sized particle with an antibody might require the attachment of an IgG antibody that is roughly equal in size. By comparison, a fluorescent material that might be useful for localization of a targeted nanoparticle such as green fluorescent protein (GFP) is about 5 nm. Derivitization strategies for the construction of targeted nanoparticles must incorporate a consideration of potential steric conflicts for incorporation of targeting, detection, and therapeutic components. Other chapters in this text will extensively examine derivitization technologies for nanoparticles.

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