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

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/gFe 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 Dy3+-doped magneto-liposomes.