Magnetic nanoparticles covered with polycyclic aromatic hydrocarbons as singlet oxygen carriers for combining photodynamic therapy and magnetic hyperthermia

Abstract

We developed hybrid nanoparticles consisting of a magnetic core (zinc-doped iron oxide – IONP:Zn) and a polycyclic aromatic hydrocarbon (PAH) shell (naphthalene-@Naph or anthracene-@Anth) to improve cancer and infectious disease therapies. PAHs are employed as shell material due to their ability to capture, store, and deliver singlet oxygen (1O2) on demand and under relatively controlled conditions. The magnetic core is aimed at generating heat via magnetic hyperthermia (MHT). The PAH layer will be responsible for trapping 1O2ex-situ (loading), carrying it into the tumor cells, and releasing 1O2in situ upon the heating caused by the magnetic core. We characterized the nanoparticles by Dynamic Light Scattering, X-ray diffraction, transmission electron microscopy, and fluorescence spectroscopy. Results indicate that IONP:Zn was successfully synthesized and covered with either anthracene or naphthalene. Both shells could trap 1O2 produced ex-situ by methylene blue (MB), but the IONP:Zn@Naph presented the highest 1O2 trapping efficiency. Fluorescence spectroscopy suggested the cycloreversion reaction and the consequent 1O2 release only when the nanoparticles' temperature increases above 40 °C. Cytotoxicity experiments using E. coli bacterial growth curves revealed that the IONP:Zn@Naph NPs loaded with 1O2 are not intrinsically toxic at 37 °C. However, when heated to temperatures above 40°, they caused a decreased bacterial growth. Maximum toxicity occurs at 44 °C. Considering that the IONP:Zn@Naph nanoparticles presented a higher 1O2 release temperature (≥40°C) compared to soluble naphthalene derivatives (≥37°C) and that the human basal temperature is ∼37°C, the IONP:Zn@Naph requires temperatures for 1O2 release that is high enough for not releasing 1O2 before achieving the target, and feasible to be reached by magnetic hyperthermia. Therefore, these nanodevices are promising for developing new cancer and infectious disease therapies.