Laser-triggered combined chemotherapy and photodynamic therapy enabled by iron sulfide-doxorubicin@bovine lactoferrin nanozymes for breast cancer therapy

Background: The use of magnetic nanozymes with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. Results: Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide nanozymes containing doxorubicin (FeS-Dox@bLf NZs) by wet chemical synthesis that can respond to tumor acidity. Then, the physicochemical properties of synthesized NZs were investigated by TEM, SEM, DLS and spectroscopic methods. Likewise, the level of Fe 2+ release, H 2 S and Dox from FeS-Dox@Lf NZs under acidic conditions was evaluated. It was observed that Fe 2+ and S 2- caused significant OH and H 2 S release through the Fenton reaction. Also, the toxic effects of FeS-Dox@Lf NZs on 4T1 cancerous cells were investigated by MTT and flow cytometry assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. Conclusion: Overall, FeS-Dox@Lf nanozymes with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.