Biocompatible graphene nanosheets tethered with poly-gamma glutamic acid for anticancer therapy

Abstract

Here, I report that poly gamma glutamic acid (-PGA)-modified graphene could improve hemocompatibility and biocompatibility for enhanced in vivo safety and therapeutic index of graphene-based nanomedicine. Phenylalanine-grafted -PGA (amphiphilic -PGA , APGA) was synthesized and coated on reduced graphene oxide (rGO) via non-covalent interaction resulting APGA-coated rGO (ArGO). Modification of APGA on rGO did not interrupt photothermal activity of rGO, showing similar increase of temperature upon near-infrared (NIR) laser irradiation. ArGO revealed prolonged dispersion stability under physiological fluids over 4weeks whereas rGO in a plain form or physical mixture with -PGA was immediately deposited under same conditions. Although rGO in a plain form or physical mixture with -PGA form aggregation with red blood cells from at a rGO dose of 31mg/l ArGO showed much higher hemocompatibility upto rGO dose of 250 mg/l. Adding of -PGA did not decrease acute lethal rate of rGO, resulting 0 % survival rate at a rGO dose of 50 mg/kg, however, ArGO showed 100% survival rate of animals after intravenous injection at a same dose. Systemic administration of ArGO facilitated prolonged blood retention of rGO over 8 h post-dosing and significantly enhanced tumor accumulation in SCC7 tumor-bearing mice at 24 h post-dosing as compared with rGO-treated mice which resulting temperature increase to 50.2 ± 0.7oC at tumor sites upon NIR laser irradiation. Single irradiation of ArGO-treated mice revealed tumor ablation effect whereas tumor volumes of untreated and rGO-treated mice rapidly grew. Our results provides an evidence that biocompatible graphene via non-covalent modification of APGA would potentiate clinical applications of graphene-based nanomedicine.