Melinte Georgian Alin STMA Anul II Biomaterial-Nanoparticle Hybrid Systems: Synthesis, Properties, and Applications Melinte Georgian Alin STMA Anul II

Fig. 1 Electrostatic stabilization of metal colloid particles Fig.1 Electrostatic stabilization of metal colloid particles. Attractive van der Waals forces are outweighed by repulsive electrostatic forces between adsorbed ions and associated counterions at moderate interparticle separation.

Fig. 2 Antibody Structure Several fundamental features show biomaterials to be important future building blocks for nanoparticle architectures Biomaterials reveal specific and strong complementary recognition interactions, e.g., antigen-antibody, nucleic-acid-DNA, hormone-receptor → self-assembly. Various biomaterials include several binding sites, e.g., the two Fab-sites of antibodies. This allows the multidirectional growth of nanoparticle structures. Fig. 2 Antibody Structure

Enzymes provide catalytic tools for the manipulation of biomaterials Enzymes provide catalytic tools for the manipulation of biomaterials. The use of biocatalysts for the replication of biomaterial- nanoparticle conjugates may provide an effective system for the formation of nanostructures of pre-designed shapes and compositions. Proteins may be genetically engineered and modified with specific anchoring groups. This facilitates the aligned binding to nanoparticles, or the site-specific linkage of the biomaterial to surfaces. Consequently, directional growth of nanoparticle structures may be dictated.

Fig. 3 The conceptual generation of nanoparticle - biomaterial conjugates and their assembly to give functional devices.

The Synthesis of Biomaterial–Functionalized Nanoparticles Functionalization by Electrostatic Adsorption biomolecules ranging from low-molecular-weight organic substances (e.g., vitamin C) to large protein/enzyme molecule the simplest case: nanoparticles that are stabilized by anionic ligands such as carboxylic acids (citrate, tartarate, lipoic acid), the adsorption of proteins originates from electrostatic interactions

The electrostatic deposition of proteins or enzymes + an oppositely charged polyelectrolyte polymer => protein/polymer multilayer shell (hundreds of nanometers in thickness). This strategy permits the preparation of functional films with a high density of enzyme molecules on nanoparticles. Fig. 4 The assembly of nanoparticle-protein conjugates by electrostatic interactions

2. Functionalization by Chemisorption of Thiol-Derivatized Biomaterials strong chemisorption of proteins on nobel metal nanoparticles can originate from the binding of thiol groups (from cysteine residues) existing in the proteins (e.g., immunoglobulins, serum albumin) to the nanoaprticles surface. If no such residues are available in the native proteins, thiol groups can be incorporated by chemical means or by genetic engineering. Fig. 5 The formation of nanoparticle-protein conjugates by the adsorption of nanoparticles on A natural, and B synthetic thiol groups of the protein.

3. Functionalization by Specific Interactions Anchor groups such as, disulfides, phosphane ligands, or thiols are often used for the binding of the bifunctional linkers to Au, Ag, CdS, and CdSe nanoparticles. These anchor groups readily substitute weakly adsorbed molecules stabilizing the nanoparticles, or may be incorporated in the nanoparticle synthesis, resulting in a nanoparticle surface providing functional groups for further reactions These structures provide unique synthetic routes for the covalent binding of a single target biomolecule per nanoparticle. By covalently attaching proteins to nanoparticle surfaces, problems of instability, reversibility and inactivation can be overcome.

Fig. 6 The assembly of nanoparticle-biomaterial conjugates by the use of bio-affinity interactions, A by the use of streptavidin-biotin interactions, and B by the use of antibody-antigen interactions.

Receptor-Induced Aggregation of Guest-Functionalized Nanoparticles Protein-based recognition systems can be used to organize inorganic nanoparticles into network-aggregates, for instance with the interaction between D-biotin and the biotin-binding protein streptavidin. The recognition between water-soluble biotin and the homotetrameric protein Sav is characterized by an extraordinary affinity constant of Ka > 1014 M-1, which makes it the strongest ligand-receptor binding interaction presently known.

Fig. 7 The use of biotin-streptavidin interactions to build nanoparticle networks, A using streptavidin to link biotin-functionalized nanoparticles, and B using a biotin dimer to link streptavidin-functionalized nanoparticles. C The use of streptavidin-linked thioated biotin to build nanoparticle networks.

Properties and Applications of Nanoparticle-Biomaterial Composites The functionalization of nanoparticles with biomolecules results in changes in the properties of the nanoparticles and their interactions with the environment. e.g. : -adsorption of vitamin C on TiO2 nanoparticles, the optical properties of the particles were red shifted by 1.6 eV; -the solubility of nanoparticles in water can be greatly improved by the functionalization of their surfaces with highly hydrophilic biomolecules;

-alteration of the chemical properties of the biomolecules covering nanoparticles by external signals (e.g., electrical, optical) can be used to control interactions of the modified nanoparticles with the environment, for example, to control the binding of a secondary modifier or the aggregation of the nanoparticles; -small molecules and polymers can affect the chemical reactivity of biomolecules; if there are several possible parallel reactions, the effect produced by a promoter/inhibitor on a specific chemical reaction can change the effective chemical path of the whole process, resulting in a regulation of the biochemical system;

The Aggregation of Biomaterial-Functionalized Nanoparticles The organization and patterning of inorganic nanoparticles into two- and threedimensional (2D and 3D) functional structures is a fundamental prerequisite for the assembly of chemical, optical, magnetic and electronic devices. Methods of obtaining 2D and 3D arrays of metal and semiconductor nanoparticles: solvent evaporation of hydrophobic colloids random inclusion of the nanoparticles into gels and glassy matrices template-directed synthesis at structured surfaces in porous protein crystals or bacterial superstructures chemical coupling in solution by means of bivalent crosslinker molecules.

Ther advantages of utilizing biomaterials as building blocks of nanoparticle structures 1. The diversity of biomaterials facilitates the selection of building units of predesigned size, shape and functionality. 2. The availability of chemical and biological means to modify and synthesize biomaterials, e.g., synthesis of nucleic acids of predesigned composition and shape, eliciting monoclonal antibodies, or modifying proteins by genetic engineering

3. Enzymes may act as biocatalytic tools for the manipulation of the biomaterials. 4. Hydrolysis of proteins, scission or ligation of DNA or replication of nucleic acids may be employed as assembler tools of nanoparticle architecture through the manipulation of the biomaterial. 5. Crosslinking nanoparticles with enzyme units may generate biocatalytic assemblies of pre-designed functionality. These different features of the biomaterial crosslinking units provide the flexibility for the generation of nanoparticle structures of tunable physical, chemical and functional properties.

References: 1. Gunter Schmid, Nanoparticles: From Theory to Application, (2004) WILEY-VCH Verlag GmbH & Co. KGaA. 2. Philippe Knauth, Joop Schoonman, NANOSTRUCTURED MATERIALS Selected Synthesis Methods, Properties and Applications, (2004) Kluwer Academic Publishers