Design of Green-Synthesized Dy3+-Doped Iron Oxide Nanoparticle-Entrapped Liposomes for Synergistic Modulation of MRI Contrast, Magnetic Hyperthermia, and Combined Anticancer Efficacy.

Abstract

Cancer treatment demands the development of multifunctional diagnostic tools and therapeutic agents with low toxicity and a high therapeutic index. The current work aimed to design multifunctional quercetin (QTN)-encapsulated Dy³⁺-doped magneto-liposomes as theranostic agents. Fe₃O₄ and Dy³⁺-doped Fe₃O₄ nanoparticles were synthesized with the aid of Punica granatum L fruit peel extract. The thin film hydration technique employed to encapsulate Dy³⁺-doped iron oxide nanoparticles (IONPs) in liposomes resulted in a small multilamellar vesicle size of ∼50 nm. The antioxidant capacity of QTN-encapsulated liposomes displayed improved efficacy and better radical oxygen scavenging (ROS) ability. The saturation magnetization initially increased upon Dy³⁺ addition, followed by a significant reduction at higher Dy³⁺ concentrations due to the formation of a mixed phase. Magnetic hyperthermia studies on Dy³⁺-doped magneto-liposomes revealed a superior heating efficiency of ∼95.0 ± 5.9 W/g_Fe at a biomedically relevant field-frequency range. Dy³⁺-doped magneto-liposomes increased both T₁ and T₂ contrast, especially with Dy³⁺ playing an effective role to shorten T₂. The presence of Dy³⁺ in magneto-liposomes induced an enhanced X-ray attenuation of ∼22.7 HU. In vitro studies on MG-63 cell lines envisaged better efficacy against cancer cells (∼20%), while negligible cytotoxicity has been revealed from tests conducted on noncancerous HEK293 cells. The results clearly showed the multimodal theranostic applications of quercetin-loaded Dy^3+-doped magneto-liposomes.