Co-delivery of cisplatin and doxorubicin by carboxylic acid functionalized poly (hydroxyethyl methacrylate)/reduced graphene nanocomposite for combination chemotherapy of breast cancer cells

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, pi-pi stacking and hydrogen bonding. The obtained nanocomposite was uptake by MCF-7 cells at early first hour because of nanocomposite small size (below 70 nm). Cell viability assay results revealed that the Dox&Cis-loaded nanocomposite showed the highest rate of MCF-7 cells at lowest concentration (IC50 = 0.798 mu g/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 drug-loaded 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.

Automated summary

A novel pH-responsive magnetic nanocomposite based on reduced graphene oxide was developed for combined delivery of Dox and Cis to MCF-7 cells, displaying high cytotoxicity. The nanocomposite's unique structure allowed for simultaneous encapsulation of Dox and Cis, leading to apoptosis in the cells.