Background: Various types of cancer therapy strategies have been investigated and successfully applied so far. There are a few modern strategies for improving drug selec- tivity and biocompatibility, such as nanoparticle-based drug delivery systems. Herein, we designed the traceable enzyme-conjugated magnetic nanoparticles to target human breast cancer cells by simulating the innate immune cell’s respiratory explosion response. Methods: The human immune cell simulated anti-breast cancer-nanorobot (hisABC- NB) was produced by conjugating the mouse-derived iNOS and human-originated MPO enzymes on the folate-linked chitosan-coated Fe3 O4 nanoparticles. The synthe- sized nanoparticles were functionalized with folic acid as the breast cancer cell detec- tor. Then, the hisABC-NB’s stability and structural properties were characterized by studying Zeta-potential, XRD, FTIR, VSM, FESEM, and DLS analysis. Next, the selectivity and anti-tumor activity of the hisABC-NB were comparatively analyzed on both normal (MCF-10) and cancerous (MCF-7) human breast cells by analyzing the cells’ survival, apoptotic gene expression profile (P53, BAX, BCL2), and flow cytometry data. Finally, the hisABC-NB’s traceability was detected by T2-weighted MRI imaging on the balb-c breast tumor models. Results: The hisABC-NB significantly reduced the MCF-7 human breast cancer cells by inducing apoptosis response and arresting the cell cycle at the G2/M phase compared with the normal cell type (MCF-10). Moreover, the hisABC-NB exhibited a proper MRI contrast at the tumor region of treated mice compared with the non-treated type, which approved their appropriate MRI-mediated traceability. Conclusion: The hisABC-NB’s traceability, dirigibility, and selective cytotoxicity were approved, which are the three main required factors for an efficient anticancer com- pound. Therefore, it has the potential to be used as an intelligent safe anticancer agent for human breast cancer treatment. However, several in vitro and in vivo studies are required to clarify its selectivity, stability, and safety.

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