Nanoparticle-based biologic mimetics

Abstract

Centered on solid chemistry foundations, biology and materials science have reached a crossroad where bottom-up designs of new biologically important nanomaterials are a reality. The topics discussed here present the interdisciplinary field of creating biological mimics. Specifically, this discussion focuses on mimics that are developed using various types of metal nanoparticles (particularly gold) through facile synthetic methods. These methods conjugate biologically relevant molecules, e.g., small molecules, peptides, proteins, and carbohydrates, in conformationally favorable orientations on the particle surface. These new products provide stable, safe, and effective substitutes for working with potentially hazardous biologicals for applications such as drug targeting, immunological studies, biosensor development, and biocatalysis. Many standard bioanalytical techniques can be used to characterize and validate the efficacy of these new materials, including quartz crystal microbalance (QCM), surface plasmon resonance (SPR), and enzyme-linked immunosorbent assay (ELISA). Metal nanoparticle-based biomimetics continue to be developed as potential replacements for the native biomolecule in applications of immunoassays and catalysis.

FIGURE 1

Modified Brust reaction scheme for polar ligands.

FIGURE 2

Examples of thiolate ligands used in the synthesis of water-soluble Au monolayer-protected clusters (MPCs). (a) tiopronin, (b) glutathione, (c) 4-mercaptobenzoic acid, (d) 1-thio-β -D-glucose, (e) N, N, N-trimethyl (mercaptoundecyl)ammonium (TMA).

FIGURE 3

Scheme of the thiol place-exchange reaction. The stoichiometry of the incoming to exiting ligand is 1:1.

FIGURE 4

Chart of the different rates at which place exchange and (possibly) migration occur. (Reprinted, with permission, from Ref. . Copyright 1999 American Chemical Society.)

FIGURE 5

The noncovalent interaction based place-exchange reaction. (Reprinted, with permission, Wiley Periodicals, Inc.)

FIGURE 6

The quartz crystal microbalance (QCM) biosensor showing an antibody recognizing a functionalized nanoparticle (antigen mimic). (Reprinted, with permission, Wiley Periodicals, Inc.)

FIGURE 7

Comparison of the glutathione (a) and tiopronin (b) ligands used to functionalize MPCs. Tiopronin is a truncated form of the 3-amino acid glutathione, with overlap shown in red. (Reprinted, with permission, from Ref. . Copyright 2005 American Chemical Society.)

FIGURE 8

Different nanostructures used: (a) the 3-D GSH-MPC, (b) the 3-D 10-amino acid hemagglutinin monolayer-protected clusters (HA-MPC), and (c) the same 10-amino acid sequence for HA as a 2-D self-assembled monolayer (SAM) with tiopronin spacers. (Reprinted, with permission, from Ref. . Copyright 2005 American Chemical Society.)

FIGURE 9

Step-by-step creation of the conformational mimic nanoparticle using the synthetic protective antigen (PA) peptide.

FIGURE 10

Loop presenting MPCs (left) shown compared to the native protein (middle) and the linear presenting monolayer-protected cluster (MPC) (right). (Reprinted, with permission, Wiley Periodicals, Inc.)

FIGURE 11

Model of Au₅₅ clusters irreversibly bound to the grooves of DNA. (Reprinted, with permission, Wiley Periodicals, Inc.)

FIGURE 12

Hydroxy- and imidazole-functionalized nanoparticles working together to catalyze silica formation. The ligands used to functionalize the particles are shown in (a), while the interaction between particles in (b) and (c). Part (d) shows the stepwise synthetic route of the ligands. (Reprinted, with permission, Wiley Periodicals, Inc.)