Modeling the interaction of polymeric nanoparticles functionalized with cell penetrating peptides at the nano-bio interface

Abstract

The interaction of nanoparticles with Caco-2 monolayers in cell culture underpins our predictions of the uptake of nanoformulations in vivo for drug delivery. Cell-penetrating peptides (CPP), such as oligoarginine, are currently of interest to enhance cellular uptake of bioactives and nanoparticles. This paper assesses the cellular association of poly(ethyl-cyanoacrylate) nanoparticles functionalized with di-arginine-histidine (RRH) in a Caco-2 cell model. We applied a computational model of particokinetics, In vitro Sedimentation, Diffusion and Dosimetry (ISDD) to predict the accumulation of nanoparticles on the cell surface. An important finding is that the proportion of nanoparticles associated with cells was less than 5 %. This has important implications for interpreting nanoparticle uptake in vitro. RRH-decoration does not appear to alter nanoparticle deposition, but increases association of nanoparticles with Caco-2 cells. Immediate deposition of nanoparticles on the cell surface was apparent and similar between formulations, but underestimated by the ISDD model. Key to understanding the nano-bio interface for drug delivery, nanoparticles that reach the cells were not necessarily absorbed by them, but can become detached. This variable of nanoparticle release from cells was incorporated into a new mathematical model presented here.

Keywords: Caco-2 cells; Cell uptake; Cellular association; Nanoparticle accumulation; Nanoparticle detachment; Poly(ethyl-cyanoacrylate) nanoparticles.