Fishing to Design Inherently Safer Nanoparticles - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 276

Figure 20.1 Overview of tiered design scheme to probe nanoparticle biological interactions. Tier 1:
rapid toxicity screening. Tier 2: cellular toxicity and distribution. Tier 3: molecular expression.
NBI knowledge base. Tier 2 involves further testing of those nanoparticles identified
in tier 1 as eliciting significant adverse effects. This involves probing for potential
cellular targets and modes of action utilizing transgenic fluorescent zebrafish, assays
to evaluate the oxidative environment, cell death, and biodistribution of the nano-
particles. Nanoparticles are then grouped by structural indices in tier 3, where gene
expression profiles are defined. These data are also reported to the NBI knowledge
base. Ultimately, the combination of data obtained from each tier of discovery will
provide a path toward defining structure-activity relationships (SARs).
A key component necessary for defining a structure-activity relationship is
to begin with well-characterized nanoparticles. There are currently many methods
to create nanoparticles, but there exists no standard guiding the collection or