title: Small rigid platforms functionalization with quaternary ammonium: targeting extracellular matrix of chondrosarcoma.
abstract: 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.
  
  
  BACKGROUND
  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.
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France. Electronic address: elisabeth.noirault@inserm.fr.
authors: Elisabeth
authors: E
authors: Miot-Noirault
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Aurélien
authors: A
authors: Vidal
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France.
authors: Jessica
authors: J
authors: Morlieras
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France.
authors: Pauline
authors: P
authors: Bonazza
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Philippe
authors: P
authors: Auzeloux
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Sophie
authors: S
authors: Besse
authors: Département d'anatomo-pathologie, Centre Jean Perrin, 63000 Clermont-Ferrand, France.
authors: Marie-Mélanie
authors: MM
authors: Dauplat
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Caroline
authors: C
authors: Peyrode
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Françoise
authors: F
authors: Degoul
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, 69000 Lyon, France.
authors: Claire
authors: C
authors: Billotey
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France.
authors: François
authors: F
authors: Lux
authors: UMR S957 INSERM, Nantes Atlantique Universités, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses primitives, 44000 Nantes, France.
authors: Françoise
authors: F
authors: Rédini
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France.
authors: Olivier
authors: O
authors: Tillement
authors: UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Jean-Michel
authors: JM
authors: Chezal
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, 69000 Lyon, France.
authors: David
authors: D
authors: Kryza
authors: Institut Lumière Matière, UMR 5306 Université Lyon1-CNRS, Université de Lyon, 69622 Villeurbanne cédex, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, 69000 Lyon, France.
authors: Marc
authors: M
authors: Janier
mesh_terms: D064751:Ammonium Compounds / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy / Q000378:metabolism*; D005109:Extracellular Matrix; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012833:Siloxanes / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D064751:Ammonium Compounds; D012833:Siloxanes; D005682:Gadolinium
keywords: Chondrosarcoma; Nanoparticles; Proteoglycans; Targeting