1 - Engineering critical nanoscale design parameters (CNDPs): A strategy for developing effective nanomedicine therapies and assessing quantitative nanoscale structure-activity relationships (QNSARs)

Abstract

This account begins with a brief historical overview of dendrimer-based atom/protein mimicry and dendritic effects all of which provided a window to the concept of nanoperiodicity. Nanoperiodicity embraces all periodic property relationships associated with nanoparticles that are dependent on six critical nanoscale design parameters (CNDPs); namely: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. All well-defined hard/soft nanoparticles, especially dendrimers, exhibit important CNDP directed property patterns. These quantitative CNDP relationships provide a powerful strategy for engineering and assessing quantitative nanoscale structure-activity relationships (QNSARs). Important dendrimer-based QNSAR examples related to nanomedicine are known in the literature and several are presented in this account. Recent QNSAR examples published in the last 5 years are reviewed. This is followed by an in depth examination of a dendrimer-based CNDP engineering study to identify an optimum candidate for use as an antiviral agent against influenza A (i.e., Spanish flu; H1N1). This study and other dendrimer-based targeted drug delivery examples reveal the critical importance of using high quality, defect free, monodispersed dendrimer samples for all QNSAR studies. This chapter is concluded by introducing a recent initiative to better define quality assurance of all nanoparticles, as well as dendrimers used in bio-nanoscale investigations. This initiative is referred to as Minimum Information Reporting in Bio-Nano Experimental Literature (MIRIBEL). This new initiative may portend new minimum characterization requirements for all nanoparticles used in peer reviewed publications.