Thermosensitive/superparamagnetic iron oxide nanoparticle-loaded nanocapsule hydrogels for multiple cancer hyperthermia

Magnetic hyperthermia therapy (MHT) has been explored as an efficient and non-invasive treatment for cancer. However, the short retention time of magnetic nanoparticles localized within tumor targets hinders its potential for repeatable treatment. We report herein on the development of an injectable, biodegradable, thermosensitive and superparamagnetic iron oxide nanoparticle-loaded nanocapsule hydrogels (SPION-NHs) system for multiple MHT and long-term magnetic resonance imaging (MRI) contrast. Transmission electron microscopic images showed the core-shell structure of self-assembled poly(organophosphazene) nanocapsules and multiple embedded SPIONs within the core. The SPION-loaded nanocapusule solution can be transformed into hydrogel form at body temperature via the hydrophobic interaction. The cancer cells were killed efficiently using multiple MHT at moderate temperature through necrosis, as compared to single MHT-induced apoptosis. More than three weeks retention of SPIONs within tumors after a single injection of SPION-NHs facilitated successful multiple MHT, which was monitored by T2-weighted MRI. Furthermore, excellent in vivo anti-cancer effect was observed after four cycles of MHT without severe damage on the surrounding healthy tissues, which was in contrast to single magnetic thermal ablation.