ZnFe2O4@L-cysteine-N/RGO as efficient nano-sonosensitizers, pH-responsive drug carriers and surface charge switchable drug delivery system for targeted chemo-sonodynamic therapy of cancer

Chemo-sonodynamic therapy (CSDT) utilizes Ultrasound (US) responsive and pH generation of reactive oxygen species (ROS) (O2, OH, H2O2) from magnetic ZnFe2O4 nano-sonosensitizers (NSSs). It can be considered as an effective procedures to treat some cancer along with chemotherapy. In this work we designed CSDT exhibiting pH/US-responsive drug release through acidic pH (5.5) and ROS generation from Curcumin (Cur)-loaded ZnFe2O4@L-cysteine‑nitrogen-doped reduced graphene oxide (N/RGO) nano-carriers. Finally, the generation of free radicals and their combination with chemotherapy increases the effectiveness of cancer treatment. In this study, a straightforward method by which could be functionalized surface of ZnFe2O4 NSSs via L-cysteine or cysteine (L-Cys or Cys) for anti-cancer Cur delivery was developed. Cur was linked to the surface of as-fabricated ZnFe2O4@L-Cys through covalent bond. Apart from being a standard thiol stabilizer, L-Cys is eco-friendly, good water-soluble, and biocompatible making it a very effective capping ligand for ZnFe2O4 NSSs. The present study deals with obtaining a targeted drug delivery system making use of CSDT. To raise the drug encapsulation efficiency and specificity of drug uptake by cancer cells, ZnFe2O4 NSSs functionalized and loaded with L-Cys and N/RGO. The ZnFe2O4@L-Cys NPs size on the N/RGO nanosheets surface was about 50 nm. The DLE value was reached 63.17 % and 71.65 % for ZnFe2O4@L-Cys and ZnFe2O4@L-Cys-N/RGO, respectively at 24 h. The amount of Cur release in ZnFe2O4@L-Cys-N/RGO nanocarrier under US irradiation and pH 5.5 condition was higher than pH 7.4 environment and without US irradiation.