Surface-functionalized ultrasmall superparamagnetic nanoparticles as magnetic delivery vectors for camptothecin.
Drug-nanoparticle conjugates: The anticancer drug camptothecin (CPT) was covalently linked at the surface of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) via a linker, allowing drug release by cellular esterases. Nanoparticles were hierarchically built to achieve magnetically-enhanced drug delivery to human cancer cells and antiproliferative activity.The linking of therapeutic drugs to ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) allowing intracellular release of the active drug via cell-specific mechanisms would achieve tumor-selective magnetically-enhanced drug delivery. To validate this concept, we covalently attached the anticancer drug camptothecin (CPT) to biocompatible USPIOs (iron oxide core, 9-10 nm; hydrodynamic diameter, 52 nm) coated with polyvinylalcohol/polyvinylamine (PVA/aminoPVA). A bifunctional, end-differentiated dicarboxylic acid linker allowed the attachment of CPT to the aminoPVA as a biologically labile ester substrate for cellular esterases at one end, and as an amide at the other end. These CPT-USPIO conjugates exhibited antiproliferative activity in vitro against human melanoma cells. The intracellular localization of CPT-USPIOs was confirmed by transmission electron microscopy (iron oxide core), suggesting localization in lipid vesicles, and by fluorescence microscopy (CPT). An external static magnetic field applied during exposure increased melanoma cell uptake of the CPT-USPIOs.
Cengelli
Feride
F
Centre Hospitalier Universitaire Vaudois and University of Lausanne, University Institute of Pathology, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland.
Grzyb
Justyna A
JA
Montoro
Auxia
A
Hofmann
Heinrich
H
Hanessian
Stephen
S
Juillerat-Jeanneret
Lucienne
L
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004950:Esterases / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008280:Magnetics; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission; D011145:Polyvinyls / Q000737:chemistry; D013499:Surface Properties; D013997:Time Factors
D000970:Antineoplastic Agents; D005290:Ferric Compounds; D011145:Polyvinyls; C534904:polyvinylamine; C000499:ferric oxide; D004950:Esterases; D002166:Camptothecin