d-Fructose-Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

Macromol Biosci. 2017 Aug;17(8). doi: 10.1002/mabi.201600502. Epub 2017 Apr 3.

Abstract

The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d-fructose decoration of 16% renders the polymers water-soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA-MB-231 breast cancer cells. Therefore, the introduction of d-fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent.

Keywords: cell-type specific uptake; d-fructose, poly(ethylene imine); nonviral gene delivery; triple-negative MDA-MB-231 breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Cell Line, Tumor
  • Female
  • Fructose* / chemistry
  • Fructose* / pharmacology
  • Gene Transfer Techniques*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Polyethyleneimine* / chemistry
  • Polyethyleneimine* / pharmacology

Substances

  • Fructose
  • Polyethyleneimine