Small rigid platforms functionalization with quaternary ammonium: targeting extracellular matrix of chondrosarcoma

Nanomedicine. 2014 Nov;10(8):1887-95. doi: 10.1016/j.nano.2014.06.011. Epub 2014 Jun 25.


This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA were increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma.

From the clinical editor: In this study, gadolinium-based complexing DOTA-surfaced small polysiloxane nanoparticles were functionalized with quaternary ammonium derivatives that target the extracellular matrix of chondrosarcoma. The authors demonstrate in a rat model that the use of these constructs results in a 40% increase of tumor accumulation and retention compared to non-functionalized (and otherwise same) platforms. Similar approaches would be welcome additions to the clinical armamentarium addressing chondrosarcoma.

Keywords: Chondrosarcoma; Nanoparticles; Proteoglycans; Targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Compounds / chemistry*
  • Ammonium Compounds / therapeutic use
  • Animals
  • Cell Line, Tumor
  • Chondrosarcoma / drug therapy
  • Chondrosarcoma / metabolism*
  • Extracellular Matrix
  • Gadolinium / chemistry
  • Humans
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Siloxanes / chemistry
  • Xenograft Model Antitumor Assays


  • Ammonium Compounds
  • Siloxanes
  • Gadolinium