Prolonged blood circulation and enhanced tumor penetration of biomimetic magnetic nanoemulsion for improved magnetic hyperthermia in combination with immunotherapy

The low delivery efficiency of magnetic nanoparticles (MNPs) to tumors via intravenous injection greatly limited the therapeutic efficacy of magnetic hyperthermia therapy (MHT) against tumor due to the short blood circulation and poor tumor penetration of MNPs. Here, we describe a general strategy to improve the delivery efficiency of MNPs to tumors by magnetic field (MF) and ultrasound (US). Biomimetic nanoemulsions were developed by encapsulating perfluorohexane, iron oxide nanoparticles (IONPs) and imiquimod within red blood cell membrane. When administrated intravenously in vivo, the biomimetic nanoemulsions can evade uptake and extend their blood circulation. They rapidly target the site of the tumor by magnetic targeting and trigger drug release due to the phase transformation of perfluorohexane under US stimulation. The concomitant bubble cavitation under the US generates microstreaming, thereby facilitating the penetration of IONPs into the tumor tissue. When MHT is combined with immunotherapy, improved efficacy against both primary and metastatic tumors and the growth inhibition of distant tumors were demonstrated. We believe this strategy provides a general solution for MNPs delivery to tumor through intravenous administration, thereby holding the promise in improving the therapeutic efficacy and reducing potential side effects of MHT.