Carboplatin prodrug conjugated Fe3O4 nanoparticles for magnetically targeted drug delivery in ovarian cancer cells

Abstract

Platinum (Pt)-based drugs including cisplatin, carboplatin and oxaliplatin have been widely used as first-line anticancer regimens due to their excellent anticancer efficacy. However, the clinical application of these drugs is greatly limited due to their side effects and drug resistance. In this study, an antitumor drug delivery system based on carboplatin prodrug loading Fe₃O₄ nanoparticles (NPs@carboplatin) was developed and the antitumor activity was also investigated. The as-synthesized NPs@carboplatin has an average diameter of 7.88 nm with a zeta potential of 8.11 mV. It exhibited a higher cytotoxic effect than carboplatin on both A2780 (cisplatin sensitive) and A2780DDP (cisplatin resistant) ovarian cancer cells via MTT assay, which can overcome Pt resistance. Moreover, the nanoparticles (NPs) loaded with carboplatin possess excellent delivery capability, which can be effectively taken up by ovarian cancer cell lines through an endocytosis process. With excellent delivery capability as carriers, NPs@carboplatin can promote drug internalization and result in the increase of intracellular drug accumulation with enhanced cellular cytotoxicity. Furthermore, in vivo experiments demonstrated that NPs@carboplatin can be widely distributed into major organs, and in the presence of an external magnetic field, the Fe₃O₄ nanocarrier is beneficial to visualize the tumor site location and promote the subsequent antitumor efficacy. It revealed a relatively high tumor inhibition rate without obvious potential toxicity to normal organs. Taken together, these results indicate that the magnetically targeted NPs@carboplatin can act as a drug delivery system and will have great potential in ovarian cancer therapeutic applications.