A pH-Responsive Yolk-Like Nanoplatform for Tumor Targeted Dual-Mode Magnetic Resonance Imaging and Chemotherapy

Incorporation of T₁ and T₂ contrast material in one nanosystem performing their respective MR contrast role and simultaneously serving as an efficient drug delivery system (DDS) has a significant potential application for clinical diagnosis and chemotherapy of cancer. However, inappropriate incorporation always encountered many issues, such as low contact area of T₁ contrast material with water-proton, inappropriate distance between T₂ contrast material and water molecule, and undesirable disturbance of T₂ contrast material for T₁ imaging. Those issues seriously limited the T₁ or T₂ contrast effect. In this work, we developed a yolk-like Fe₃O₄@Gd₂O₃ nanoplatform functionalized by polyethylene glycol and folic acid (FA), which could efficiently exert their tumor targeted T₁-T₂ dual-mode MR imaging and drug delivery role. First, this nanoplatform possessed a high longitudinal relaxation rate (r₁) (7.91 mM^-1 s^-1) and a stronger transverse relaxation rate (r₂) (386.5 mM^-1 s^-1) than that of original Fe₃O₄ (268.1 mM^-1 s^-1). Second, cisplatin could be efficiently loaded into this nanoplatform (112 mg/g) and showed pH-responsive release behavior. Third, this nanoplatform could be effectively internalized by HeLa cells with time and dosage dependence. Fourth, the FA receptor-mediated nanoplatform displayed excellent T₁-T₂ dual mode MR contrast enhancement and anticancer activity both in vitro and in vivo. Fifth, no apparent toxicity for vital organs was observed with systemic delivery of the nanoplatform in vivo. Thus, this nanoplatform could be a potential nanotheranostic for tumor targeted T₁-T₂ dual-mode MR imaging and chemotherapy.