ROS, pH, and magnetically responsive ZnFe2O4@l-Cysteine@NGQDs nanocarriers as charge-reversal drug delivery system for controlled and targeted cancer chemo-sonodynamic therapy

[Display omitted] •Zeta potential results showed the pH-responsive charge-reversal drug delivery system.•MTT results presented ZnFe2O4@l-Cysteine@NGQDs is a non-toxic carrier.•ZnFe2O4@l-Cysteine@NGQDs have great potential in chemo-sonodynamic therapy.•CSDT-based combination therapies show good synergistic effects.•Ultrasound-triggered controlled release of ZnFe2O4@l-Cysteine@NGQDs nano-carriers was demonstrated for 96 h. In this study, we designed ZnFe2O4 nano-sonosensitizers (NSSs) was achieved through coating with biocompatible l-Cysteine (Cys) and nitrogen-doped graphene quantum dots (NGQDs). ZnFe2O4 @Cys@NGQDs nanocarrier was showed change of surface charge (in cancer cells) as well as the enhancement of the sonocatalytic property (for the production of radicals) by external and internal stimuli, with pH and ultrasound (US), respectively. The results show the increase in the anticancer activity of Curcumin (Cur) using ZnFe2O4@Cys@NGQDs as an effective drug delivery system in chemo-sonodynamic therapy (CSDT). The results of the in vitro cytotoxic assay show a significant inhibition of A549 cells by ZnFe2O4@Cys@NGQDs-Cur compared to the free form of Cur. The Cur drug loading efficiency of nano-carriers were as high as 61.3 % w/w for ZnFe2O4@Cys) and 72.2 % w/w for ZnFe2O4@Cys-NGQDs. The value of Cur release with US radiation after 96 h for ZnFe2O4@Cys@NGQDs-Cur at pH = 5.5 was 89.17 %, which was higher than the value of release under the same conditions at pH = 7.4 (72.21 %).