Solid-state materials have played such a significant role in the development of humankind that we now mark the passage of time with terms such as Iron Age and Bronze Age. Still today there is no shortage of materials needs, yet the landscape of possible solid-state inorganic compounds is almost incomprehensively vast. How can we possibly hope to find the perfect combination of atoms for the materials so desperately needed for advanced fuel cell technology, hydrogen production, etc., if each composition is to be explored one-by-one or even using the best high-throughput screening methods available?

Nature has provided some of the best examples of materials synthesis. Nearly every living organism on Earth synthesizes a solid-state material, some for structural integrity or protection, others for biosphere function such as light focusing or magnetotaxis. The remarkable ability of biological organisms to construct inorganic materials has inspired research aimed at understanding and mimicking the growth of biominerals. We have asked the question: Can biomolecules evolve in vitro in response to certain selection criteria until they are capable of forming a solid-state material with a desired property? The answer is yes. The Pt cubes shown below are one example. These were grown in the presence of an RNA sequence that recognizes the precursor complex [Pt₂(DBA)₃] (DBA is dibenzylideneacetone) and mediates the morphology of the growing crystals. This sequence was isolated from a large random RNA sequence (~10¹⁴ unique sequences) specifically because of its ability to mediate crystal growth.

Pt particles synthesized in the presence of specific RNA sequences grow with cubic morphology.

This is an image taken by the Nanohunter of nanoparticles grown on a surface containing an RNA sequence that controls particle nucleation and growth. The pipet is delivering reverse transcription primer to a single particle in order to isolate and amplify the RNA attached to a specific particle of interest.

Polyvalent interactions are ubiquitous in biology. The valency of a particle (protein, virus, cell, gold nanoparticle, etc.) is the number of connections it can make with another particle. The attachment of viruses and bacteria to cells are just two examples in biology of interactions that occur via polyvalency. It has been proposed that biological systems exploit polyvalent interactions because they allow an organism to take advantage of an existing set of monovalent (and perhaps weak) ligands rather than evolving completely new, higher affinity ligands for a given function. Indeed, polyvalent interactions can be very favorable; binding of a trivalent oligosaccharide ligand to its asialoglycoprotein cell surface receptor occurs with a binding constant of 10⁸ M^-1 even though the binding constant of the corresponding monovalent interaction is only 10³ M^-1.

The Feldheim group is studying polyvalent binding interactions between ligand-stabilized gold nanoparticles and cells. Gold was chosen as a platform from which to build synthetic polyvalent binders because it is size tunable (we study particles with diameters of 1.5 nm, 2.0 nm, 3.0 nm, 10 nm, and 20 nm) and gold surfaces may be modified with nearly any thiol-containing small molecule or polymer. We have synthesized gold nanoparticles modified with oligonucleotides (ssDNA, dsDNA, ssRNA), viral peptides (HIV tat), and even small molecule drugs (HIV drugs). Moreover, combinations of two or more chemically distinct ligands can be attached to a single nanoparticle to impart multiple functions. The ability to create mixed monolayers on a nanoscale platform provides a powerful tool that can be used to improve water solubility, tune sterics, and control cellular internalization. For example, the Feldheim group has shown that gold nanoparticles modified with mixed monolayers of a classic receptor-mediated endocytic peptide and a nuclear localization peptide were able to target the nucleus of a HepG2 cell line from outside the cell. Either peptide alone was incapable of delivering the nanoparticle into the cell nucleus. We have also demonstrated recently that the number of particles taken up per cell increases as the number of peptides per particle increases. This type of polyvalent interaction may be useful in delivering therapeutics into cells and cell nuclei with higher selectivity and efficiency.