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

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 (Mn^II) is a highly attractive element due to its paramagnetic property with a high coordination number. However, Mn^II does not lead to the efficient self-assembly of DHBCs because of the relatively high aqueous solubility of coordinated Mn^II. This article reports a facile method for direct conjugation of Mn^II 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 Mn^II enables a large number of polyvalent Mn^II 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 Mn^II-loaded polymeric nanoparticles (Mn^II-PNPs) possess nanogel-like scaffolds, which allow for efficient water permeation at the Mn^II-incorporated interior for enhanced magnetic resonance contrasting effect. Additionally, by comparing the coordination properties of Mn^II and cisplatin, we endeavor to understand the internal structures and the relevant physicochemical features of metal-chelated nanoparticles.