In vitro biological activities of anionic gamma-Fe2O3 nanoparticles on human melanoma cells.
Three magnetic fluid (MF) samples containing gamma-Fe2O3 (maghemite) nanoparticles surface-coated with either meso-2,3-dimercaptosuccinic acid (DMSA), citric acid or lauric acid were prepared, characterized, and assessed for their cytotoxic potential on the human SK-MEL-37 melanoma cell line. Ultra-structural analysis was also performed using transmission electron microscopy (TEM). In vitro cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory concentration (IC50) derived from the sigmoidal dose response curve was 254 microg-iron/mL (95% confidence interval 239-270 microg-iron/mL) for lauric acid-coated nanoparticles. DMSA-coated nanoparticles did not exhibit a clear trend toward toxicity (IC50 value is more than 2260 +/- 50 microg-iron/mL) and the IC50 value was about 433 +/- 14 microg-iron/mL for citric-acid coated nanoparticles. The cytotoxic response correlated with both the hydrodynamic diameter and the zeta potential suggests that the chain length of the carboxylic acid of the coating species may influence metabolic cellular process. Also the assayed nanoparticles can be considered non-cytotoxic to human melanoma cells since IC50 values are higher than plasma concentration usually observed in clinical use of contrast agents. Using TEM we verified that all assayed nanoparticles were internalized by cells through endocytic vesicles. Additionally, cells treated with lauric acid-coated nanoparticles at high concentration (588 or 840 microg-iron/mL) displayed morphological features of apoptosis (surface blebbing, intense vacuolization and chromatin condensation) or a typical DNA ladder pattern when analyzed by TEM or agarose gel electrophoresis, respectively. Apoptotic events may be operative, suggesting a promising therapeutic application for the lauric acid-coated nanoparticle in the treatment of cancer cells.
Departamento de Bioquímica e Biologia Molecular Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia-GO 74001-970, Brazil.
Erika Regina Leal
ER
de Freitas
Paula Roberta Otaviano
PR
Soares
Rachel de Paula
Rde P
Santos
Regiane Lopes
RL
dos Santos
Joel Rocha
JR
da Silva
Elaine Paulucio
EP
Porfirio
Sônia N
SN
Báo
Emilia Celma de Oliveira
EC
Lima
Paulo César
PC
Morais
Lidia Andreu
LA
Guillo
D000838:Anions; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000473:pathology*; D053768:Metal Nanoparticles; D008855:Microscopy, Electron, Scanning; D014961:X-Ray Diffraction
D000838:Anions; D005290:Ferric Compounds; C000499:ferric oxide