Lipid polymer hybrid nanoparticles as targeted drug delivery system for melanoma treatment

Synthesis of lipid polymer hybrid nanoparticles which express vitamin D receptors.

Abstract

Our understanding of the biologic effects (including toxicity) of nanomaterials are incomplete. In vivo animal studies remain the gold standard; however, widespread testing remains impractical, and the development of in vitro assays that correlate with in vivo activity has proven challenging. Here, we demonstrate the feasibility of analysing in vitro nanomaterial activity in a generalizable, systematic fashion. We assessed nanoparticle effects in a multidimensional manner, using multiple cell types and multiple assays that reflect different aspects of cellular physiology. Hierarchical clustering of these data identifies nanomaterials with similar patterns of biologic activity across a broad sampling of cellular contexts, as opposed to extrapolating from results of a single in vitro assay. We show that this approach yields robust and detailed structure–activity relationships. Furthermore, a subset of nanoparticles was tested in mice, and nanoparticles with similar activity profiles in vitro exert similar effects on monocyte number in vivo. This data suggests a strategy of multidimensional characterization of nanomaterials in vitro that can inform the design of novel nanomaterials and guide studies of in vivo activity.