Ferrimagnetic mPEG--PHEP copolymer micelles loaded with iron oxide nanocubes and emodin for enhanced magnetic hyperthermia-chemotherapy.

As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy (MHT) under alternating magnetic field (AMF) is a clinically promising thermal therapy. However, the poor heating conversion efficiency and lack of stimulus-response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) (mPEG--PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin (denoted as EMM). Besides an enhanced magnetic resonance (MR) contrast ability (  = 271 mM s) due to the high magnetization, the specific absorption rate (2518 W/g at 35 kA/m) and intrinsic loss power (6.5 nHm/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents (Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage (10 μg Fe/mL), and the tumors on mice are completely eliminated after the combined MHT-chemotherapy.