Zinc ferrite nanoparticle with enhanced magnetic attraction for controlled drug delivery and in vivo tumor therapy

Iron oxide nanoparticles (IONPs) have been widely applied in drug delivery systems for tumor-targeting over the past decade. However, their efficacy in remote control and targeting by magnetic attraction is still limited by insufficient magnetic force. Herein, we introduce non-toxic zinc ferrite NPs (ZFNPs) with strong magnetism as enhancers for tumor-targeting. They were encapsulated in larger poly lactic-co-glycolic acid (PLGA) NPs together with the anticancer drug, SN38 resulting in ZFNP-containing magnetic NPs (ZMNPs). Upon magnetic attraction, the cellular uptake of ZMNPs increased by 15.43 times compared to treatment without a magnet. This was remarkable because the NP-encapsulating traditional IONPs (MNPs) showed only 2.47 times increase. In vivo biodistribution analysis in SCC7 tumor-bearing mice revealed that magnetic attraction enhanced the tumor accumulation of ZMNPs by 3.9 times. Furthermore, ZMNPs exhibited antitumor effects by reducing the tumor volume to 214 mm³ with magnetic attraction, whereas it was 1016.7 mm³ without it. These results demonstrate that the enhanced magnetism of ZMNPs led to improved tumor targeting, resulting in superior therapeutic outcomes compared to traditional MNPs. We expect that these small ZFNPs could be encapsulated in other types of NPs with various structures, suggesting their universal potential for enhanced tumor-targeting.