Functionalized Graphene Oxide with Hepatocyte Targeting as Anti-Tumor Drug and Gene Intracellular Transporters

Abstract

In order to realize the hepatocyte-specific targeted delivery of anti-tumor drug and gene, lactosylated chitosan oligosaccharide (LCO) functionalized graphene oxides (GO-LCO) containing quaternary ammonium groups (GO-LCO+) were prepared. The formation and composition of GO-LCO+ were confirmed by FTIR, AFM, TGA and zeta-potential. The in vitro cells uptakes of this functionalized GO were investigated and the results showed that GO-LCO+ can deliver fluorescein FAM-labeled DNA sequence (FAM-DNA) into human hepatic carcinoma cells (QGY-7703) with higher efficiency than positively charged chitosan oligosaccharide (CO) functionalized graphene oxides (GO-CO+) without Lactose acid modification. The loading efficiency of doxorubicin chloride (Dox) on GO-LCO+ with 477 µg/mg was obtained at the initial Dox concentration of 0.45 mg/ml and release of Dox on GO-LCO+ showed strong pH dependence. The toxicity of GO-LCO+ before and after loading with Dox toward QGY-7703 cells was further investigated. Our results suggest the functionalized GO to be used as a nanocarrier for hepatocyte targeted co-delivery of anti-tumor drugs and genes with low cytotoxicity, promising for future applications in anticancer drug and gene combined therapy.

Specific capture of glycosylated graphene oxide by an asialoglycoprotein receptor: a strategic approach for liver-targeting

“…Similar behavior was described by Cao et al, 20 who previously described the presence of a new prominent band at 1639 cm À1 corresponding to the stretching mode of amide groups by the conjugation of GO with lactosylated chitosan. Also, Sarkar et al 21 reported the occurrence of a new absorption band at 1630 cm À1 due to the modication of GO with aminated molecules.…”

Self-Assembly of Organic Nanomaterials and Biomaterials: The Bottom-Up Approach for Functional Nanostructures Formation and Advanced Applications

“…Due to their special physico-chemical characteristics and electronic properties, the graphene can yield various applications, including batteries, light emitting diodes and supercapacitors [220,221]. Moreover, biomedical applications of graphene include bio-medical imaging and anticancer drug delivery [222,223]. Recently, graphene oxide (GO) nanocarriers functionalized with lactosylated chitosan oligosaccharide was constructed for the targeted drug delivery of doxorubicin drug and DNA sequences into the (human) hepatic carcinoma cells (QGY-7703) [223].…”

“…Moreover, biomedical applications of graphene include bio-medical imaging and anticancer drug delivery [222,223]. Recently, graphene oxide (GO) nanocarriers functionalized with lactosylated chitosan oligosaccharide was constructed for the targeted drug delivery of doxorubicin drug and DNA sequences into the (human) hepatic carcinoma cells (QGY-7703) [223]. The maximal loading capacity of the drug and fluorescein amidites labeled DNA (FAM-DNA) reached 477 µg/mg and 4 mmol/g, respectively.…”

“…The maximal loading capacity of the drug and fluorescein amidites labeled DNA (FAM-DNA) reached 477 µg/mg and 4 mmol/g, respectively. The nanocarrier was able to deliver the complex to the specific site (i.e., QGY-7703) for over 30 min, while no significant toxicity has been detected, even at the high concentration of 100 µg/mL [223].…”

Fabrication and Antitumor Mechanism of a Nanoparticle Drug Delivery System: Graphene Oxide/Chitosan Oligosaccharide/γ‐Polyglutamic Acid Composites for Anticancer Drug Delivery

“…Cao et al. synthesized CO and lactose acid functionalized GO for loading DOX and FAM‐labeled DNA . Abbasian et al.…”