Development of Aminated Chitosan-Functionalized Magnetite Nanoparticles Enriched with Zinc Phthalocyanine: Detailed Photophysical and Model Cell Membrane Studies

Abstract

Stimuli-induced anticancer therapies based on remotely activated nanoagents have drawn a great deal of attention as attractive alternatives to conventional therapies. The rapid development of nanomaterial functionalization in the past few decades has allowed for the tailoring of hybrid nanoagents with dual anticancer activity and the simultaneous application of two complementary stimuli-triggered therapies, enhancing a therapeutic effect. In this study, the synthesis and characterization of the novel aminated chitosan-coated magnetite nanoparticles (MNPs) with zinc(II) phthalocyanine (ZnPc) immobilized on their surface are presented. The synthetized ZnPc-MNPs combine the superparamagnetic properties of MNPs and the photosensitizing potential of ZnPc, which makes them promising nanomaterials with application potential in dual anticancer therapy based on hyperthermia and photodynamic effects. To understand and describe the mechanism of the ZnPc-MNPs action at the molecular level, we used a variety of surface approaches. Analytical techniques provided information on the structure, morphology, and size of the obtained ZnPc-MNPs. The stationary and time-resolved spectroscopy methods showed that the immobilization of the photosensitizer on the MNP surface boosts its photophysical parameters important from a photodynamic therapy point of view. Because of the decrease in the fraction of excitation energy exchange into heat of the ZnPc-MNPs, the singlet oxygen generation quantum yield increased to 0.57, improving its anticancer activity. Moreover, it was shown that ZnPc immobilized on the MNP surface does not aggregate even despite aggregation of the ZnPc-MNPs. As a result, ZnPc preserves its spectral properties beneficial for a photosensitizer. Finally, the effect of the ZnPc-MNPs on model cell membranes formed by applying a Langmuir technique was studied. The studies performed indicate that the MNPs introduced into the phospholipid monolayer at low concentrations do not significantly disturb its thermodynamic state, or the domain structure, which is promising in terms of their biocompatibility.