Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy

Engineering the protein corona (PC) on nanodrugs is emerging as an effective approach to improve their pharmacokinetics and therapeutic efficacy, but conventional in vitro pre-programmed methods have shown great limitation for regulation of the PC in the complex and dynamic in vivo physiological environment. Here, we demonstrate an magnetothermal regulation approach that allows us to in situ modulate the in vivo PC composition on iron oxide nanoparticles for improved cancer nanotherapy. Experimental results revealed that the relative levels of major opsonins and dysopsonins in the PC can be tuned quantitatively by means of heat induction mediated by the nanoparticles under an alternating magnetic field. When the PC was magnetically optimized in vivo, the nanoparticles exhibited prolonged circulation and enhanced tumor delivery efficiency in mice, 2.53-fold and 2.02-fold higher respectively than the control. This led to a superior thermotherapeutic efficacy of systemically delivered nanoparticles. In vivo magnetothermal regulation of the PC on nanodrugs will find wide applications in biomedicine.