Preparation and Characterization of Iron Oxide Nanoparticles for Effective Epirubicin Delivery to Drug Resistant Breast Cancer Cells
Preparation and Characterization of Iron Oxide Nanoparticles for Effective Epirubicin Delivery to Drug Resistant Breast Cancer Cells
Sayra Tariq, Zeeshan Mutahir and Moazzam Ali*
ABSTRACT
Chemoresistance is toughest of all challenges in the fight against cancer. The incorporated drugs are pumped out of the cells due to a number of reasons. However, if these drugs are attached to nanoparticles, they are likly to be retained by the cells for longer period of time. In this study, iron oxide nanoparticles were synthesized using green synthesis and studied for their drug release and anticancer properties. Scanning electron microscope (SEM) analysis results showed that the average size of the synthesized spherical iron oxide nanoparticles was around 48nm, which was further confirmed with transmission electron microscopy (TEM) images. Anticancer drug, epirubicin was attached to the iron oxide nanoparticles. Immobilization of epirubicin on the nanoparticles was confirmed by FTIR analysis (Fourier-transform infrared spectroscopy). The spherical nanoparticles showed rapid pH sensitive drug release at pH 4.9 (pH of the cancer cell) targeting the tumor microenvironment and the cancer cell or endosomes/lysosomes. Drug loaded nanoparticles showed increased zones of inhibition as compared to naked iron oxide nanoparticles. After adsorbing on the nanoparticle surface, the loaded drug exhibited potent cytotoxic effect on drug sensitive (wt) and epirubicin resistant (epi-R) breast cancer cell lines MDA-MB-231 in a dose dependent manner. MDA-MB-231/ epi R cells showed viability of 71.59% against 20 µM epirubicin, however it decreased to 58.19% when the cells were exposed same concentration of epirubicin loaded on Iron oxide nanoparticles. The pattern of increased efficacy of drug loaded nanoparticles was observed in wound healing assay carried out with both MDA-MB-231/wt and epirubicin resistant cells. Percentage healing after 24 h with 10µM epirubicin alone was 38.1% for MDA-MB-231/epi-R cells. This further decreased to 32.35% when cells were exposed to 10µM epirubicin loaded on iron oxide nanoparticles. This study shows the ability of iron oxide nanoparticle-based drug delivery system for carrying the drug, and effectively releasing it for drug sensitive as well as drug resistant breast cancer cells.
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