Folic acid-modified Laponite®-stabilized Fe3O4 nanoparticles for targeted T2-weighted MR imaging of tumor

Abstract

In this study, a targeted T2-weighted MR imaging agent based on laponite (LAP) was constructed for cancer cells overexpressing folate receptors. Firstly, LAP stabilized Fe3O4 NPs are synthesized by a controlled co-precipitation route, and then amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG-COOH) is assembled on the surface of LAP/Fe3O4 NPs to provide additional stability, followed by the conjugate of folic acid modified generation 2 polyamidoamine dendrimer (G2-FA) via EDC coupling chemistry. The formed LAP/Fe3O4-PLA-PEG-G2-FA NPs can display good colloidal stability and an enhanced r2 relaxivity of 327.6 mM−1 s−1. In vitro experiments demonstrate that the hybrid nanoparticles are cytocompatible in the studied concentration range, and could specific target cancer cells with FA receptors overexpression. Finally, the xenografted tumor model experiment verifies that LAP/Fe3O4-PLA-PEG-G2-FA NPs can significantly reduce the MR signal of tumor site by specific accumulation, and be metabolized from the mice within 24 h. Therefore, LAP/Fe3O4-PLA-PEG-G2-FA NPs with good biocompatibility, a high r2 relaxivity, and FA targetability show a huge potential as a targeted T2-weighted MR imaging contrast for the early diagnosis of tumors overexpressing FA receptors.