Folic acid-conjugated graphene oxide as a transporter of chemotherapeutic drug and siRNA for reversal of cancer drug resistance

Functionalized graphene oxide (GO) with folic acid-conjugated chitosan oligosaccharide (FACO) containing quaternary ammonium groups (GO-FACO + ) was successfully prepared. The formation and composition of GO-FACO + were confirmed by FTIR, UV–Vis, AFM, TGA, and zeta-potential. Cell experiments show that cellular uptake of fluorescein FAM-labeled DNA sequence (FAM-DNA) delivered by GO-FACO + exhibits higher efficiency in doxorubicin chloride (Dox)-resistant MCF-7 human breast cancer cells (MCF-7/Dox) with folate receptor overexpressed than that delivered by chitosan oligosaccharide (CO)-functionalized graphene oxides (GO-CO + ) without folic acid modification and in human lung cancer A549 cells with folate receptor negatively expressed. The loading efficiency of Dox on GO-FACO + was 568.4 μg mg −1 at the initial Dox concentration of 0.5 mg mL −1 , and in vitro release of Dox showed strong pH dependence. MDR1 siRNA transfected by GO-FACO + could efficiently knockdown the MDR1 mRNA and P-gp expression levels in MCF-7/Dox cells. GO-FACO + shows no obvious toxicity even at 500 μg mL −1 . The sequential deliveries of MDR1 siRNA and Dox by GO-FACO + exhibited much higher cytotoxicity against MCF-7/Dox cells than only delivery of Dox by GO-FACO + when Dox concentration is lower than 25 μg mL −1 , while excess 80 % cells were killed in the two cases when Dox concentration is higher than 30 μg mL −1 . Taken together, this functionalized GO has potential applications for targeted intracellular delivery of anti-tumor drugs and genes.