| In this study a novel pH-responsive magnetic nanocomposite
based on reduced graphene oxide was developed for combination
of doxorubicin (Dox)-cisplatin (Cis) delivery to destroy the
MCF-7 cell line. For this purpose, polyhydroxyethyl methacrylate
(PHEMA) was bonded to the reduced graphene oxide through
ATRP polymerization using grafting from method. Then the
PHEMA hydroxy groups were converted to succinyloxy groups by
polyesterification with succinic anhydride. The physicochemical
properties of the nanocomposite were investigated via FTIR, SEM,
XRD, DLS and TGA analysis. Unique structure of nanocomposite
led to simultaneous encapsulation of Dox (75%) and Cis (82%)
through ionic interaction, p–p stacking and hydrogen bonding.
The obtained nanocomposite was uptake by MCF-7 cells at early
first hour because of nanocomposite small size (below 70nm).
Cell viability assay results revealed that the Dox&Cis-loaded nanocomposite
showed the highest rate of MCF-7 cells at lowest concentration
(IC50¼0.798 mg/mL) compared to treatment groups
received single drug-loaded nanocomposite and free drugs.
Dox&Cis-loaded nanocomposite exhibited a synergistic influence
with the combination index (CI) value <1. The cell cycle analysis
results revealed that the highest amount of apoptosis (cells population
in sub G1 was 75%) was observed in the Dox&Cis-loaded
nanocomposite treatment group compared with the single drugloaded
nanocomposite and free drugs. Our findings confirmed
that combinational therapy by Dox and Cis graphene oxide-based
nanocomposite has increased the cytotoxicity in MCF-7 cells by
stimulating the apoptotic response. |