Enhancing <SUP>29</SUP>Si Hyperpolarization Efficiency in Silica Nanoparticles via Multishell Design with Selective <SUP>29</SUP>Si-Isotope and Radical Enrichment

Abstract

Silica nanoparticles (SiO2 NPs) are garnering significant attention in medical imaging as promising probes for hyperpolarized 29Si magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Dynamic nuclear polarization (DNP) is crucial for amplifying 29Si MR signals by transferring polarization from electron spins to nuclei under microwave irradiation. However, the hyperpolarization of SiO2 NPs is limited by the absence of intrinsic electronic defects. To improve hyperpolarization, we designed multilayered SiO2 NPs (core@shell@shell) with selective 29Si isotope and TEMPO radical enrichment in specific shell layers or throughout the particle, enabling solvent-free direct-polarization DNP-magic angle spinning. This design effectively improved the 29Si hyperpolarized signal compared to conventional particles, with homogeneous enrichment providing the highest signal enhancement up to 25 times in direct-polarization DNP. Spin diffusion length in the enriched samples ranged from 0.6 to 1.4 nm, with hyperpolarization occurring primarily in the radical-enriched regions. Thus, the positioning and density of the enriched 29Si nuclei relative to the radicals are critical for augmenting the hyperpolarization. These designed nanoparticles facilitate in-depth analysis of both surface and core regions, eliminating the need for radical removal, preserving hyperpolarization, and positioning them as promising candidates for 29Si MRI probes.