Phthalocyanine iron nanodots for combined chemodynamic-sonodynamic cancer therapy

Sonodynamic therapy (SDT) is a new non-invasive treatment method that has received widespread attention due to its deep tissue penetration and high safety. However, the low sonodynamic efficiency of sonosensitizers makes SDT poorly effective and limits its bioapplication. Therefore, it is urgent to prepare safe and highly efficient sonosensitizers. Herein, a new kind of sonosensitizer, iron phthalocyanine nanodots (FePc NDs), is fabricated via a facile thermal organic-phase synthesis procedure for enhanced SDT against cancer. Due to the presence of Fe, FePc NDs can also be used as Fenton reagents to efficiently generate hydroxyl radicals (·OH) in the presence of hydrogen peroxide (H2O2). Notably, after modification with polyethylene glycol (PEG), FePc-PEG NDs exhibit remarkable biocompatibility and physiological stability, as well as good tumor accumulation ability. Compared with the control group, in vitro and in vivo experimental results demonstrate obvious cell killing efficiency and significant tumor suppression with the treatment of FePc-PEG NDs under ultrasound (US) irradiation. More importantly, FePc-PEG NDs have good biological safety and do not cause any adverse effects on mice. Our work highlights the use of FePc-PEG NDs as a highly effective and low-toxic sonosensitizer for enhanced SDT.