Although it has been reported that the co-delivery of drugs can be beneficial to patients to kill breast cancer cells, the delivery methods could only be employed to effectively encapsulate individual curcumin (CUR) or piperine (PIP) molecules due to their different molecular polarities. Therefore, in the current research, an attempt was made to overcome the limitation of the co-delivery of CUR and PIP nanoparticles for breast cancer therapy. To manage locoregional breast cancer recurrence, a magnetic co-delivery system of CUR and PIP against MCF-7 breast cancer cells was examined. CUR and PIP demonstrated synergistic effects for breast cancer therapy when utilized together. However, due to the different polarities of CUR and PIP, it was difficult to co-encapsulate them in conventional delivery systems. Moreover, their low bioavailability, hydrophobic nature, and low cellular uptake limit its usage for cancer therapy. In the current study, to overcome the issues and improves its therapeutic efficacy, CUR and PIP-loaded zein/chitosan-coated iron oxide (Chit-PIP/CUR-zein@Fe3O4) were prepared via a combination of anti-solvent precipitation and layer-by-layer deposition. X-ray diffraction (XRD) analysis revealed magnetite cores and also showed that the binding process did not change the Fe3O4 phase. A vibrational sample magnetometer confirmed that the saturation of sample magnetization was 60 and 40 emu/g for pure Fe3O4 and nanocomposite, respectively. Nanoparticles with an average size of 20 nm were prepared. The drug-loading content of CUR and PIP was approximately 18% and 16%, respectively. CUR and PIP release from Chit-PIP/CUR-zein@Fe3O4 was faster at the extracellular pH of around tumors (6.5) than in normal tissues (7.4), an interesting degree of pH sensitivity. The MTT assay exhibited that PIP/CUR-loaded polymeric magnetic nanoparticles had significant synergistic cytotoxicity against MCF-7 cells compared with other groups. These results demonstrate that the combination of dual-drug loaded polymeric magnetic nanoparticles holds promise for the targeted treatment of cancer cells.
