Construction of Paramagnetic Manganese-Chelated Polymeric Nanoparticles Using Pyrene-End-Modified Double-Hydrophilic Block Copolymers for Enhanced Magnetic Resonance Relaxivity: A Comparative Study with Cisplatin Pharmacophore.

Abstract

Cationic metal-mediated self-assembly of double-hydrophilic block copolymers (DHBCs) has been of great interest for the preparation of hybrid nanoparticles for versatile applications. Among many functional transition-metal ions, manganese (MnII) is a highly attractive element due to its paramagnetic property with a high coordination number. However, MnII does not lead to the efficient self-assembly of DHBCs because of the relatively high aqueous solubility of coordinated MnII. This article reports a facile method for direct conjugation of MnII ions inside sterically stabilized polymer assemblies, composed of pyrene-end-modified DHBCs. Nitroxide-mediated radical polymerization was used to prepare the poly(ethylene glycol)- b-poly(acrylate) DHBC precursor, followed by the end-modification with pyrene maleimide via the radical-exchange reaction. Employing the self-associated DHBC as the nanoscale template, the simple addition of MnII enables a large number of polyvalent MnII ions to be immobilized at the chelating blocks of DHBCs, which can be readily monitored by the excimeric fluorescence emission change of the terminal pyrene fluorophore. The resulting MnII-loaded polymeric nanoparticles (MnII-PNPs) possess nanogel-like scaffolds, which allow for efficient water permeation at the MnII-incorporated interior for enhanced magnetic resonance contrasting effect. Additionally, by comparing the coordination properties of MnII and cisplatin, we endeavor to understand the internal structures and the relevant physicochemical features of metal-chelated nanoparticles.