Synergistic co-delivery of doxorubicin and melittin using functionalized magnetic nanoparticles for cancer treatment: loading and in vitro release study by LC–MS/MS

Abstract

In this study, citric acid-functionalized Fe3O4 magnetic nanoparticles (CA-MNPs) were prepared via a coprecipitation method and were fully characterized. Doxorubicin (DOX) and melittin (MEL), as anticancer agents, were loaded onto CA-MNPs surface through electrostatic interactions with the aim to achieve an effective co-delivery system for cancer therapy. The loading efficiency and in vitro release profiles of DOX and MEL were investigated by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The MS/MS step was performed in the selected reaction monitoring (SRM) mode which enabled simultaneous quantification of the analytes with high specificity and sensitivity. An excellent loading efficiency of about 100% was achieved for DOX and MEL in a drug to nanocarrier ratio of 1:10. The in vitro release of the drugs from CA-MNPs was evaluated for 8 h at pH 7.4, 5.5 and 4.5. The experimental results revealed that the release behaviour of both of the anticancer agents was strongly pH-dependent and significantly enhanced at pH 4.5. The in vitro MTT assay on MCF-7 breast cancer cell line exhibited a synergistic effect between DOX and MEL which led to substantially greater antitumor efficacy, compared to single administration of these anticancer agents at equivalent doses. The results indicated that the co-delivery system of (DOX/MEL)-loaded CA-MNPs is highly capable to be used in magnetically targeted cancer therapy.