An in silico analysis of nanoparticle/cell diffusive transfer : Application to nano artificial antigen presenting cell:T-cell interaction

Abstract

Polymeric nanoparticles (nano-paAPCs) modified with T-cell antigens and encapsulating immunostimulatory or immunoinhibitory factors may act as artificial antigen-presenting cells to circulating immune cells, improving the selective delivery of encapsulated drug or cytokine to antigen-specific T-cells. Paracrine delivery of encapsulated agents from these nanoparticles to adjacent cells facilitate sustained delivery lowering the overall administered dose, thus enhancing the overall drug efficacy while reducing toxicity of pleiotropic factors. Little is known mathematically regarding the local concentration of released agent that accumulates around a nanoparticle that is near or embeds in a cell. These concentration fields are calculated here in an attempt to understand paracrine efficacy of these nano-paAPC systems. The significant factor accumulation that can occur if the particles were to embed in the cell membrane may explain observed experimental data regarding enhanced T-cell activation and nanoparticle-mediated improvement in the drug delivery process to noninternalizing cellular targets.

Graphical Abstract

Biodegradable nanoparticles (nano-paAPC’s) impregnated with Interlukin-2 (IL-2) and surface modified with stimulatory and co-stimulatory T-cell ligands have been found to be efficient artificial antigen-presenting cells for T-cells. The present work is an attempt to better understand the efficacy of these particles by calculating the local IL-2 concentration as a function of the secretion characteristics of the nano-paAPC and particle/cell spacing. The potentially significant IL-2 accumulation found here, especially if the nano-paAPCs embed in the cell membrane, may explain observed experimental data regarding enhanced T-cell activation and nanoparticle-mediated improvement in the drug delivery process to non-internalizing cellular targets.