title: Synthesis of chemically functionalized superparamagnetic nanoparticles as delivery vectors for chemotherapeutic drugs.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are in clinical use for disease detection by MRI. A major advancement would be to link therapeutic drugs to SPIONs in order to achieve targeted drug delivery combined with detection. In the present work, we studied the possibility of developing a versatile synthesis protocol to hierarchically construct drug-functionalized-SPIONs as potential anti-cancer agents. Our model biocompatible SPIONs consisted of an iron oxide core (9-10 nm diameter) coated with polyvinylalcohols (PVA/aminoPVA), which can be internalized by cancer cells, depending on the positive charges at their surface. To develop drug-functionalized-aminoPVA-SPIONs as vectors for drug delivery, we first designed and synthesized bifunctional linkers of varied length and chemical composition to which the anti-cancer drugs 5-fluorouridine or doxorubicin were attached as biologically labile esters or peptides, respectively. These functionalized linkers were in turn coupled to aminoPVA by amide linkages before preparing the drug-functionalized-SPIONs that were characterized and evaluated as anti-cancer agents using human melanoma cells in culture. The 5-fluorouridine-SPIONs with an optimized ester linker were taken up by cells and proved to be efficient anti-tumor agents. While the doxorubicin-SPIONs linked with a Gly-Phe-Leu-Gly tetrapeptide were cleaved by lysosomal enzymes, they exhibited poor uptake by human melanoma cells in culture.
authors.affiliation: Université de Montréal, Department of Chemistry, PO Box 6128, Station, Centre-ville, Montreal, Que., Canada H3C 3J7. stephen.hanessian@umontreal.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Grzyb
authors.forename: Feride
authors.initials: F
authors.lastname: Cengelli
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D052203:Ferrosoferric Oxide; D006801:Humans; D008545:Melanoma / Q000188:drug therapy; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; C001943:5-fluorouridine; D004317:Doxorubicin; D014529:Uridine; D052203:Ferrosoferric Oxide