Enhancing ²⁹Si Hyperpolarization Efficiency in Silica Nanoparticles via Multishell Design with Selective ²⁹Si-Isotope...

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.