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Nanomedicine. 2015 May;11(4):1019-28. doi: 10.1016/j.nano.2014.12.019. Epub 2015 Jan 31.

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

Author information

1
Ansama Research, 5 Highview Ct., Wayne, NJ, USA. Electronic address: mlabowsky@aol.com.
2
Yale University, Department of Biomedical Engineering, 55 Prospect St. Malone Engineering Center, New Haven, CT, USA. Electronic address: jlowenthal@aya.yale.edu.
3
Yale University, Department of Biomedical Engineering, 55 Prospect St. Malone Engineering Center, New Haven, CT, USA; Yale University, Department of Chemical Engineering, 10 Hillhouse Avenue, Mason Laboratory, New Haven, CT, USA; Yale University School of Medicine, Dept. of Immunobiology, New Haven, CT, USA. Electronic address: tarek.fahmy@yale.edu.

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 non-internalizing cellular targets.

FROM THE CLINICAL EDITOR:

In this interesting article, the authors utilized nanosized polymeric artificial presenting cells (nano-paAPC) that released cytokine to study the effects after interaction with T cells. It was found that nano-paAPC were able to embed into cell membrane, with subsequent enhanced T-cell activation. The findings provide further understanding of immune cell interaction and are considered to be important for designing nanoparticles engineered to deliver cytokines or immumodulatory factors to specific immune cells.

KEYWORDS:

APC; Analytical model; Artificial antigen presenting cell; Diffusion; Drug delivery; Immunotherapy; Interleukin-2; Nanoparticle; T-cell

PMID:
25652896
PMCID:
PMC6028934
DOI:
10.1016/j.nano.2014.12.019
[Indexed for MEDLINE]
Free PMC Article

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