Anti-CEA loaded maghemite nanoparticles as a theragnostic device for colorectal cancer

Abstract

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.

A Review of Surface-Enhanced Raman Spectroscopy on Potential Clinical Applications Towards Diagnosing Colorectal Cancer

“…Electron micrographs showed preferential maghemite nanoparticle uptake by CEA-expressing tumor cells and additional evidence for the specificity of the CEA-expression tumor cells was proved with ELISA and Prussian blue iron staining. Their data suggested promising results of applying a drug delivery system for targeted therapy [39]. The study of Conde et al, looked into functionalizing gold nanoparticles for specific targeting of cancer biomarkers and coating with an antibody-drug conjugate for targeted FDAapproved drugs [40].…”

Role of Raman spectroscopy and surface enhanced Raman spectroscopy in colorectal cancer

“…Another slightly different approach to using SERS for clinical use for CRC is using SERS as a characterisation/ validation tool when developing other nanoscale devices such as the work done by da Paz et al [76] (2012). In this study SERS was used as a characterisation tool in the development of maghemite nanoparticles as a theragnostic device for CRC [76] .…”

“…In this study SERS was used as a characterisation tool in the development of maghemite nanoparticles as a theragnostic device for CRC [76] . The SERS active nanoparticles used in this study were functionalised with Anti-CEA antigen in the hope that they can be used to detect primary and metastatic CRC, it was hoped by the authors that these nanoparticles could then be developed for a variety of applications including magnetic resonance imaging (MRI) enhancement and targeted drug delivery.…”

Nanotechnology in Colorectal Cancer for Precision Diagnosis and Therapy

“…Colorectal cancer (CRC) is a severe health problem and has the third-highest occurrence within the cancer-causing conditions that influence the populations of developing and developed countries (da Paz et al, 2012). Among populations of western countries, a major cause of death and morbidity is CRC (Arvelo et al, 2015).…”