Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles

Abstract

Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd3+ from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM−1S−1. Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor.