Biocompatible Nanoclusters with High Heating Efficiency for Systemically Delivered Magnetic Hyperthermia.

Despite its promising therapeutic potential, nanoparticle-mediated magnetic hyperthermia is currently limited to treatment of localized and relatively accessible cancer tumors, because the required therapeutic temperatures above 40 C can only be achieved by direct intratumoral injection of conventional iron oxide nanoparticles. To realize the true potential of magnetic hyperthermia for cancer treatment, there is an unmet need for efficient nanoparticles with high heating capacity that can efficiently accumulate at tumor sites following systemic administration and generate desirable intratumoral temperatures upon exposure to an alternating magnetic field (AMF). Although there have been many attempts to develop the desired nanoparticles, reported animal studies reveal the challenges associated with reaching therapeutically relevant intratumoral temperatures following systemic administration at clinically relevant doses. Therefore, we developed efficient magnetic nanoclusters with enhanced heating efficiency for systemically delivered magnetic hyperthermia that are composed of cobalt and manganese doped, hexagon-shaped iron oxide nanoparticles (CoMn-IONP) encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone))-based nanocarriers. Animal studies validated that the developed nanoclusters are non-toxic, efficiently accumulate in ovarian cancer tumors following a single intravenous injection, and elevate intratumoral temperature up to 44 C upon exposure to a non-invasive AMF. Moreover, the obtained results confirmed the efficiency of the nanoclusters to generate the required intratumoral temperature after repeated injections and demonstrated that nanoclusters-mediated magnetic hyperthermia significantly inhibits cancer growth. In summary, this nanoplatform is a milestone in the development of systemically delivered magnetic hyperthermia for treatment of deep-seated and metastatic cancers either alone, or in combination with other therapies.