Nanocomposites of ionic copolymer integrating Gd-containing polyoxometalate as a multiple platform for enhanced MRI and pH-response chemotherapy

摘要

This article describes the fabrication of nanosized paramagnetic drug carriers via the assembly of a pH-responsive hydrophilic block copolymer poly(polyethylene glycol methyl ether methacrylate)-b-poly(methacrylic acid-co-trimethyl ammonium bromide propyl methacrylate) (PPMT) and polyoxometalate K-13[Gd(beta(2)-SiW11O39)(2)] (GdSiW11) through electrostatic interaction. Owing to the hydrophilicity, large molecular weight, and high content of the GdSiW11 cluster bearing in the nanocomposites, the organic-inorganic nanocomposite exhibited an impressive longitudinal relaxivity as a contrast agent for magnetic resonance imaging (MRI). The surplus negative charges from the polyoxometalate cluster in the polymer nanocomposites facilitated the capture of the anti-tumor drug doxorubicin (DOX). The DOX-loaded nanocomposites were stable under the physiological environment, whereas a responsive release of DOX was achieved at pH values similar to the tumor microenvironment due to the regulation of the polyoxometalate and carboxyl groups. The DOX-loaded PPMT2-GdSiW11 nanocomposites were observed to enrich effectively at tumor sites through MRI after intravenous injection. Furthermore, the DOX-loaded composites manifested enhanced in vivo anti-tumor therapeutic efficacy and sustainable circulation time of more than 5 h, which were favourable for imaging measurement. With the advantages of the designed composite system, the present experiments propose a strategy for developing a new multiple imaging-drug delivery-local therapy platform for synergistic diagnosis and therapy.