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Background  The use of magnetic nanozymes (NZs) 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 NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe 2+ , H 2 S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular 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 NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.    Graphic abstract

Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy