High-performance PEGylated Mn-Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics

摘要

An effective magnetic nanocrystals (MNCs)-mediated theranostics strategy as a combination of simultaneous diagnostics and heating treatment of tumors by using magnetic resonance imaging (MRI) and alternating current magnetic field (ACMF) is successfully developed. In this strategy, we had firstly synthesized a well-established Mn-Zn ferrite MNCs coated with PEG-phospholipids (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol copolymers, DSPE-PEG2000). The monodisperse PEGylated MNCs with core-shell structure (15nm) exhibited excellent performance, such as high magnetism of 98emug-1 Fe, relaxivity coefficient (r2) of 338mm-1s-1, and specific absorption rate (SAR) value of 324Wg-1 Fe. It was proved that the obtained MNCs with an average diameter of 48.6nm can drastically minimize the recognition and phagocytosis of macrophages, simultaneously improve their biocompatibility invitro. These advantages endowed them with efficient passive targeting ability invivo for prominent tumor MRI and magnetically induced heating when exposed to ACMF, based on enhanced permeability and retention (EPR) effects. To ensure sufficient accumulation of MNCs within tumors for targeted hyperthermia, we described the use of MNCs with a well-tolerated intravenous single dose of 18mg Fe/kg mouse body weight, achieving repeatedly injection and hyperthermia within a subcutaneous breast cell carcinoma mouse model. With an ACMF of 12 A at 390kHz, the tumor surface sites could be heated to approximately 43°C in 30min based on MNCs-mediated intravenous injections. The long-lasting hyperthermia could effectively induce the apoptosis of tumor cells, inhibit the angiogenesis of tumor vessels, and finally suppress the tumor growth within a certain period of time.