Co-encapsulated fluorescent magnetic nanoparticles for potential applications in breast cancer therapy: Exploratory in vitro and in vivo studies

This study describes, for the first time in the literature, a suitable approach to develop co-encapsulated magnetic nanoparticles based on fluorescent biotinylated N-palmitoyl chitosan, hydrophobic magnetite, Docetaxel and Verapamil. The multicomponent nanostructures were obtained using a two-step method: ultrasonication-induced self-assembly followed by ionic gelation. Structural composition was confirmed by infrared spectroscopy; the magnetic nanostructures displayed an average hydrodynamic diameter of 322.20 ± 2.50 nm, a positive surface charge (5.63 ± 0.16 mV), good magnetic saturation (13.35 emu/g) and superparamagnetic behavior. In vitro drug release studies revealed a pH-responsive behavior for both encapsulated agents, with an enhanced release of the Verapamil. Cytotoxicity evaluation using live/dead assays on MCF-7 tumor spheroids embedded in collagen-based hydrogels demonstrated a substantial therapeutic effect. Serum interleukin-8 (IL-8) levels were quantified to evaluate systemic inflammatory responses following intravenous administration of drug free magnetic nanoparticles. IL-8 concentrations were considerably increased at day 3, indicating an acute inflammatory response, decreased during the subacute phase (days 7 and 14) and returned to control levels by day 21, demonstrating good biocompatibility. No significant toxicity was observed for magnetic nanoparticles in the rats. Overall, these findings suggest that the developed magnetic nanoplatforms represents a promising candidate for breast cancer applications and merits further in vivo investigation to elucidate the action mechanism of encapsulated therapeutics and their pharmacologic activity.