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The engineering, characterization, and application of dual-functional delivery vehicle “SPIONs–Br–FA” are reported. In this study, a citrate-coated SPIONs (superparamagnetic iron oxide nanoparticles) drug-delivery vehicle was conjugated with Br (bromelain), a phytotherapeutic anticancer agent, and finally immobilized with FA (folic acid), as a targeting moiety to the FAR+, folate receptor positive, cancer cells. Then, in vitro compatibility tests were performed to confirm the biocompatibility of the engineered system. A cytotoxicity study was carried out, which showed a significant dose advantage with SPIONs–Br–FA in reducing the IC50 values of FAR+ cancer cells compared with neat Br. Through morphological alternation studies, it was disclosed that the SPIONs–Br–FA-treated cells had undergone apoptosis, since shrinkage as well as apoptotic bodies were obviously observed. We demonstrated that SPIONs–Br–FA was a good candidate to suppress the migration of the FAR+ cancer cells as well as to inhibit colony formation of the FAR+ cancer cells compared to SPIONs–Br. We found that the apoptosis percentage was sharply increased in the FAR+ cancer cells treated by SPIONs–Br–FA compared to those treated by neat Br. Moreover, the qualitative and quantitative biodistribution study performed on the vital organs and tumor indicated a significant tumor targetability of the SPIONs–FA. Next, we demonstrated the administration of SPIONs–Br–FA through the tail vein could reduce the tumor burden in 4T1-bearing mice and also increased their lifespan when compared with SPIONs–Br and neat Br at the same concentration of bromelain. In conclusion, the results indicated that the synthesized SPIONs–Br–FA is a promising tool in the field of biomedicine, particularly in cancer therapy.

Targeted delivery of bromelain using dual mode nanoparticles: synthesis, physicochemical characterization, in vitro and in vivo evaluation