Journal
RSC ADVANCES
Volume 7, Issue 64, Pages 40074-40094Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7ra06389j
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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.
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