Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments.
New folate-conjugated superparamagnetic maghemite nanoparticles have been synthesized for the intracellular hyperthermia treatment of solid tumors. These ultradispersed nanosystems have been characterized for their physicochemical properties and tumor cell targeting ability, facilitated by surface modification with folic acid. Preliminary experiments of nanoparticles heating under the influence of an alternating magnetic field at 108 kHz have been also performed. The nanoparticle size, surface charge, and colloidal stability have been assessed in various conditions of ionic strength and pH. The ability of these folate "decorated" maghemite nanoparticles to recognize the folate receptor has been investigated both by surface plasmon resonance and in folate receptor expressing cell lines, using radiolabeled folic acid in competitive binding experiments. The specificity of nanoparticle cellular uptake has been further investigated by transmission electron microscopy after incubation of these nanoparticles in the presence of three cell lines with differing folate receptor expression levels. Qualitative and quantitative determinations of both folate nanoparticles and nontargeted control nanoparticles demonstrated a specific cell internalization of the folate superparamagnetic nanoparticles.
Sonvico
Fabio
F
UMR CNRS 8612 Physico-chimie, Pharmacotechnie, Biopharmacie--Université de Paris-Sud, Châtenay-Malabry, France.
Mornet
Stéphane
S
Vasseur
Sébastien
S
Dubernet
Catherine
C
Jaillard
Danielle
D
Degrouard
Jeril
J
Hoebeke
Johan
J
Duguet
Etienne
E
Colombo
Paolo
P
Couvreur
Patrick
P
D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry* / Q000494:pharmacology; D005334:Fever / Q000188:drug therapy*; D005492:Folic Acid / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008280:Magnetics; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D009994:Osmolar Concentration; D010316:Particle Size; D012965:Sodium Chloride; D055672:Static Electricity; D020349:Surface Plasmon Resonance
D005290:Ferric Compounds; C000499:ferric oxide; D012965:Sodium Chloride; D005492:Folic Acid