Anti-CEA loaded maghemite nanoparticles as a theragnostic device for colorectal cancer.
Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid) and surface-functionalized with anticarcinoembryonic antigen (anti-CEA) and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC) cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF) sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T) and a low-CEA expressing cell line (HCT116). Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter), dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm) and the zeta-potential (-38 mV) of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS) was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm(-1), absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116) confirm that the as-prepared MF-anti- CEA is highly specific for CEA-expressing cells. Finally, transmission electron microscopy analyses show that the association with anti-CEA seems to increase the number of LS174T cells with internalized maghemite nanoparticles, whereas no such increase seems to occur in the HCT116 cell line. In conclusion, the MF-anti-CEA sample is a biocompatible device that can specifically target CEA, suggesting its potential use as a theragnostic tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.
Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brazil.
Mariana Campos
MC
da Paz
Maria de Fátima M Almeida
Mde F
Santos
Camila M B
CM
Santos
Sebastião W
SW
da Silva
Lincoln Bernardo
LB
de Souza
Emília C D
EC
Lima
Renata C
RC
Silva
Carolina M
CM
Lucci
Paulo César
PC
Morais
Ricardo B
RB
Azevedo
Zulmira G M
ZG
Lacava
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D053769:Nanocapsules / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; C000499:ferric oxide