Sustained Nitric Oxide Release Using Hybrid Magnetic Nanoparticles for Targeted Therapy: An Investigation via Electron Paramagnetic Resonance (EPR)

This research describes the development and thorough characterization of a novel, versatile, and biocompatible hybrid nanocarrier of the NO-releasing agent NOC-18, with a specific focus on optimizing the purification process. In this study, we focused on the sustained release of NO using the biocompatible and diagnostic hybrid magnetic nanoparticles (hMNPs) containing cerium-doped maghemite (CM) NPs, embedded within human serum albumin (HSA) protein. A comprehensive study was conducted using Electron Paramagnetic Resonance (EPR) alongside the Griess assay to evaluate the NO release from the chosen NO donor NOC-18 and to assess the limitations of the molecule under various reaction conditions, identifying the optimal conditions for binding NOC-18 with minimal NO loss. Two types of particles were designed: In-hMNPs, where NOC-18 is encapsulated within the particles, and Out-hMNPs, where NOC-18 is attached onto the surface. Our results demonstrated that In-hMNPs provided a sustained and prolonged release of NO (half-life 50 h) compared to rapid release for the Out-hMNPs, likely due to the strong bonds formed with cerium, which helped stabilize the NO molecules. These results represent a promising approach to the design of the dual-function agent that combines the contrasting properties for tumor MRI with the possibility of increasing the permeability of tumor vasculature. Employment of such a dual-function agent in combination with nanotherapeutics may augment their efficacy by facilitating their access to the tumor.