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

Abstract

Incorporation of T 1 and T 2 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 T 1 contrast material with water-proton, inappropriate distance between T 2 contrast material and water molecule, and undesirable disturbance of T 2 contrast material for T 1 imaging. Those issues seriously limited the T 1 or T 2 contrast effect. In this work, we developed a yolk-like Fe 3 O 4 @Gd 2 O 3 nanoplatform functionalized by polyethylene glycol and folic acid (FA), which could efficiently exert their tumor targeted T 1 –T 2 dual-mode MR imaging and drug delivery role. First, this nanoplatform possessed a high longitudinal relaxation rate ( r 1 ) (7.91 mM –1 s –1 ) and a stronger transverse relaxation rate ( r 2 ) (386.5 mM –1 s –1 ) than that of original Fe 3 O 4 (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 T 1 –T 2 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 T 1 –T 2 dual-mode MR imaging and chemotherapy.