Conjugation of functionalized gadolinium metallofullerenes with IL-13 peptides for targeting and imaging glial tumors

Nanomedicine (Lond). 2011 Apr;6(3):449-58. doi: 10.2217/nnm.10.134.

Abstract

Background: Glioblastoma multiforme is the most common and most lethal primary brain tumor in humans, with median survival of approximately 1 year. Owing to the ability of glioma cells to aggressively infiltrate normal brain tissue and survive exposure to current adjuvant therapies, there is a great need for specific targeted nanoplatforms capable of delivering both therapeutic and imaging agents directly to invasive tumor cells.

Method: Gadolinium-containing endohedral fullerenes, highly efficient contrast agents for MRI, were functionalized and conjugated with a tumor-specific peptide and assessed for their ability to bind to glioma cells in vitro.

Results: We report the successful conjugation of the carboxyl functionalized metallofullerene Gd(3)N@C(80)(OH)(-26)(CH(2)CH(2)COOH)(-16) to IL-13 peptides and the successful targeting ability towards brain tumor cells that overexpress the IL-13 receptor (IL-13Rα2).

Conclusion: These studies demonstrate that IL-13 peptide-conjugated gadolinium metallofullerenes could serve as a platform to deliver imaging and therapeutic agents to tumor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / drug therapy*
  • Contrast Media
  • Coordination Complexes / chemistry
  • Coordination Complexes / therapeutic use*
  • Drug Delivery Systems
  • Fullerenes / chemistry
  • Fullerenes / therapeutic use*
  • Glioblastoma / diagnosis*
  • Glioblastoma / drug therapy*
  • Humans
  • Interleukin-13 / chemistry
  • Interleukin-13 / metabolism*
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Nanoshells*
  • Peptides / chemistry
  • Peptides / metabolism
  • Receptors, Interleukin-13 / metabolism
  • Rhodamines / chemistry

Substances

  • 5-carboxytetramethylrhodamine succinimidyl ester
  • Contrast Media
  • Coordination Complexes
  • Fullerenes
  • Interleukin-13
  • Peptides
  • Receptors, Interleukin-13
  • Rhodamines