Nanoparticles and antigen-specific T-cell therapeutics: a comprehensive study on uptake and release

Nanomedicine (Lond). 2015;10(7):1063-76. doi: 10.2217/nnm.14.160.

Abstract

Aim: T lymphocytes are used as cellular therapeutics in many disease entities including cancer. We investigated the uptake and retention of nanoparticles (NPs) by these nonphagocytic cells.

Materials & methods: Uptake, release and toxicity of various polymeric NP preparations were analyzed by flow cytometry, confocal laser scanning microscopy and transmission electron microscopy. T-cell effector functions were measured using IFN-γ-ELISPOT and (51)Chromium-release assays.

Results: Amino-functionalized NPs were efficiently ingested by antigen-specific T cells without adversely influencing effector functions. NPs were stored in membrane-surrounded vesicles, with major proportions released extracellularly during 24 h.

Conclusion: Amino-functionalized polymeric NPs are efficiently taken up by human T cells and could be used to design nanocarriers for direct access and manipulation of antigen-specific T cells in vivo.

Keywords: NP release; T lymphocytes; cell imaging; cellular therapy; drug delivery; endocytosis; leukemia; nanoparticles; tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Delivery Systems
  • Drug Liberation
  • Endocytosis
  • Humans
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Nanoparticles / ultrastructure
  • Polymers / chemistry
  • Polymers / metabolism*

Substances

  • Drug Carriers
  • Polymers