Iron oxide superparamagnetic nanoparticles conjugated with a conformationally blocked α-Tn antigen mimetic for macrophage activation

Nanoscale. 2014 Jul 7;6(13):7643-55. doi: 10.1039/c4nr00070f.

Abstract

Among new therapies to fight tumors, immunotherapy is still one of the most promising and intriguing. Thanks to the ongoing structural elucidation of several tumor antigens and the development of innovative antigen carriers, immunotherapy is in constant evolution and it is largely used either alone or in synergy with chemotherapy/radiotherapy. With the aim to develop fully synthetic immunostimulants we have recently developed a mimetic of the α-Tn mucin antigen, a relevant tumor antigen. The (4)C1 blocked mimetic 1, unique example of an α-Tn mimetic antigen, was functionalized with an ω-phosphonate linker and used to decorate iron oxide superparamagnetic nanoparticles (MNPs), employed as multivalent carriers. MNPs, largely exploited for supporting and carrying biomolecules, like antibodies, drugs or antigens, consent to combine in the same nanometric system the main features of an inorganic magnetic core with a bioactive organic coating. The superparamagnetic glyconanoparticles obtained, named GMNPs, are indeed biocompatible and immunoactive, and they preserve suitable characteristics for use as heat mediators in the magnetic fluid hyperthermia (MFH) treatment of tumors. All together these properties make GMNPs attracting devices for innovative tumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / immunology
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Ferric Compounds / chemistry*
  • Kinetics
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Temperature
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Ferric Compounds
  • Magnetite Nanoparticles
  • Organophosphonates
  • Tn antigen
  • Tumor Necrosis Factor-alpha
  • ferric oxide