title: 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 non-internalizing cellular targets.
  
  
  BACKGROUND
  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.
authors: Ansama Research, 5 Highview Ct., Wayne, NJ, USA. Electronic address: mlabowsky@aol.com.
authors: Michael
authors: M
authors: Labowsky
authors: Yale University, Department of Biomedical Engineering, 55 Prospect St. Malone Engineering Center, New Haven, CT, USA. Electronic address: jlowenthal@aya.yale.edu.
authors: Justin
authors: J
authors: Lowenthal
authors: 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.
authors: Tarek M
authors: TM
authors: Fahmy
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D053758:Nanoparticles; D013601:T-Lymphocytes / Q000276:immunology*
keywords: APC; Analytical model; Artificial antigen presenting cell; Diffusion; Drug delivery; Immunotherapy; Interleukin-2; Nanoparticle; T-cell
references: Microvasc Res. 2011 Nov;82(3):210-20
references: 21763328
references: Biomaterials. 2012 Oct;33(28):6634-43
references: 22749449
references: Mol Pharm. 2008 May-Jun;5(3):418-29
references: 18271547
references: Annu Rev Immunol. 1999;17:467-522
references: 10358766
references: Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Dec;78(6 Pt 1):061914
references: 19256875
references: Chem Eng Sci. 2012 May 28;74:114-123
references: 22485051
references: Mol Ther. 2008 Apr;16(4):765-72
references: 18334990
references: Mol Pharm. 2010 Apr 5;7(2):364-74
references: 20030320
references: J Drug Target. 2013 Feb;21(2):107-25
references: 22873288
references: Nat Med. 2003 May;9(5):619-24
references: 12704385
references: Biomaterials. 2007 Feb;28(5):869-76
references: 17055572
references: Biomaterials. 2012 Aug;33(23):5776-87
references: 22594972
references: Mol Pharm. 2011 Feb 7;8(1):143-52
references: 20977190
references: J Nanotechnol Eng Med. 2012 Aug;3(3):310101-310108
references: 23917171
references: J Biol Chem. 2011 Oct 7;286(40):34883-92
references: 21849500
references: Nat Mater. 2009 Jul;8(7):543-57
references: 19525947
references: ACS Nano. 2008 Mar;2(3):471-6
references: 19206572
references: PLoS One. 2012;7(12):e50265
references: 23227162
references: Conf Proc IEEE Eng Med Biol Soc. 2009;2009:1161-6
references: 19963488
references: Expert Opin Biol Ther. 2009 Apr;9(4):451-64
references: 19344282
references: Annu Rev Immunol. 2008;26:453-79
references: 18062768
references: Biomaterials. 2014 Jan;35(1):269-277
references: 24099710
references: Adv Mater. 2012 Jul 24;24(28):3757-78
references: 22528985
references: Methods Mol Biol. 2010;624:163-75
references: 20217595
references: Nat Immunol. 2008 Oct;9(10):1105-11
references: 18800163
references: Endocrinology. 2010 Feb;151(2):458-65
references: 20016026
references: ACS Nano. 2009 Jan 27;3(1):16-20
references: 19206243
references: Nano Lett. 2008 Jul;8(7):2070-6
references: 18547120
references: Nat Med. 2010 Sep;16(9):1035-41
references: 20711198
references: J Colloid Interface Sci. 2010 Mar 1;343(1):125-33
references: 20022337
references: Nanomedicine (Lond). 2013 Jul;8(7):1173-89
references: 23837856
references: Nano Lett. 2007 Dec;7(12):3716-22
references: 17983249
references: Immunity. 2008 Aug 15;29(2):238-48
references: 18674934
references: Nanomedicine. 2012 Feb;8(2):147-66
references: 21703993
references: Nanomedicine (Lond). 2012 Aug;7(8):1253-71
references: 22931450
references: Nat Biotechnol. 2004 Apr;22(4):403-10
references: 15060556
references: Adv Mater. 2012 Jul 24;24(28):3878-86
references: 22988558
references: PLoS One. 2012;7(2):e31472
references: 22328935
references: Nat Nanotechnol. 2014 Aug;9(8):639-47
references: 25086604
references: J Control Release. 2011 Sep 5;154(2):203-10
references: 21640147