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

摘要

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 Fe3O4@Gd2O3 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 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 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.