Triggered chemotherapeutic drug release from multi-component nanochains mediated by a local magnetic field

Abstract

Therapeutic efficacy was evaluated by comparing survival times of treated animals with untreated animals and control groups. The mean survival time for animals receiving a single treatment of Drug-NC followed by RF exposure was 25.1 days, compared to 15.2 days for untreated and control groups. A two-cycle treatment prolonged survival to an average of 46 days. Significant cell death was observed in the Drug-NC+RF group in histological sections of the tumors, while nearly no cell death was observed in any of the control groups. The iron oxide nanoparticles used in the chain are an effective tool for converting magnetic energy into mechanical energy. The current application makes use of restricted Brownian motion of the nanoparticles in the nanochain. The movement of the iron oxide chain is restricted due to bonding, preventing true rotation to align with the field.2 We believe the result is a mechanical “vibration” that causes imperfections in the liposome though which the drug is able to escape. To investigate this hypothesis, drug release was measured from several concentrations of Drug-NC exposed to the same magnetic field, and all samples exhibited the same release rate, suggesting that a high concentration of iron oxide nanoparticles is not necessary for drug release. Further, no global heating was observed, and the possibility of local heating was excluded through linking a fluorophore (Alexa 488) to the iron oxide chain of the Drug-NC particle.3 Multiple Drug-NC suspensions were exposed to direct heating (ΔT=0-9°C), causing a measureable decrease in fluorescence intensity. However, when the suspensions were only exposed to RF, no change in fluorescence intensity was observed.