Evaluation of anticancer effect of doxorubicin nanoparticles in 3D model of breast cancer cells

Abstract

Breast tumor is the most prevalent cancer among women worldwide. Despite significant improvement in the treatment of this disease, drug resistance and recurrence are the main obstacles for successful therapy. Aims The purpose of this study was to synthesize PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) for efficient drug delivery and targeting of doxorubicin (DOX). Further a three-dimensional cell-based model was used to evaluate the efficiency of nano formulations as an anticancer agent. Materials and methods Three-dimensional spheroids of MCF-7 cells were prepared by liquid overlay technique. Nanoparticles (NPs) were engineered by the synthesis of SPIONs, and conjugation to polyethylene glycol (PEG). DOX was loaded into PEG. The NPs were characterized physio-chemically by the means of TEM, DLS, FTIR and drug release study. The biological impact of NPs on the spheroids formed after 7 and 14 days was evaluated using MTT assay. Results Dynamic light scattering results showed that engineered NPs had a mean size of about 73 nm, with the zeta potential of 0.63. The morphology of NPS were globular and appeared to be monodisperse by the results of transmission electron microscopy. Surface modifications, were also confirmed by the results of FT-IR spectroscopy. Drug release was higher at the pH of 6.4 as compared to pH 7.4. Our analyses, confirmed the successful fabrication of 3D structure of MCF-7 cells after 7 and 14 days of culture. MTT data showed cytotoxicity of NPs on the cancer cells in the spheroids.

Discussion We have engineered a suitable drug delivery system for DOX. Such nanosystem is believed to be accumulated in the tumor site by enhanced permeation and retention (EPR) phenomenon, as well as external magnetic field. Then it can release its cargo drug in the acidic tumor microenvironment.