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Purpose: The purpose of this study was to develop magnetic nanocarriers by encapsulating magnetic nanoparticles (MNPs) and calcein or doxorubicin (DOX) into thermosensitive liposomes (TSLs), and to investigate the feasibility of visualizing them using magnetic particle imaging (MPI) and the therapeutic effect of chemotherapy using the DOX release induced by magnetic hyperthermia (MH) using tumor-bearing mice. Materials and methods: First, the TSLs were prepared using a lipid mixture composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and polyoxyethylene (20) stearyl ether (Brij78®) at a molar ratio of 96 : 4. Second, we encapsulated both MNPs and calcein into the TSLs and imaged them using our MPI scanner. The net iron concentration in the magnetic TSLs was measured by the potassium thiocyanate method. We also heated the magnetic TSLs using our system for MH. Finally, we developed TSLs encapsulating both MNPs and DOX (DOX-TSLs) and performed animal experiments. After the DOX-TSLs were administered directly into the tumors of tumor-bearing mice, the mice were scanned using our MPI scanner and then underwent MH. Results: The calcein release from the TSLs steeply increased at about 38-40°C and plateaued thereafter, whereas it was almost zero at 2736°C. The magnetic TSLs were successfully visualized using our MPI scanner. The average MPI pixel value showed significant correlations with the net iron concentration in the magnetic TSLs and the temperature rise induced by MH. When the DOX-TSLs were injected into tumors and MH was applied, the relative tumor volume growth was significantly lower than that in the case when MH was not applied, suggesting a therapeutic effect of the chemotherapy using the DOX release induced by MH. Conclusion: Our results suggest that our magnetic TSLs are useful as drug delivery nanocarriers in nanomedicine. Our results also suggest that MPI is useful for enhancing the effectiveness of chemotherapy based on the drug release from TSLs, because MPI can visualize the magnetic TSLs in positive contrast allowing us to estimate the iron concentration in the magnetic TSLs for predicting the drug release induced by MH.

Development of Magnetic Nanocarriers based on Thermosensitive Liposomes and their Visualization using Magnetic Particle Imaging