Enhancing T₁ magnetic resonance imaging contrast with internalized gadolinium(III) in a multilayer nanoparticle

Multifunctional nanoparticles for biomedical applications have shown extraordinary potential as contrast agents in various bioimaging modalities, near-IR photothermal therapy, and for light-triggered therapeutic release processes. Over the past several years, numerous studies have been performed to synthesize and enhance MRI contrast with nanoparticles. However, understanding the MRI enhancement mechanism in a multishell nanoparticle geometry, and controlling its properties, remains a challenge. To systematically examine MRI enhancement in a nanoparticle geometry, we have synthesized MRI-active Au nanomatryoshkas. These are Au core-silica layer-Au shell nanoparticles, where Gd(III) ions are encapsulated within the silica layer between the inner core and outer Au layer of the nanoparticle (Gd-NM). This multifunctional nanoparticle retains its strong near-IR Fano-resonant optical absorption properties essential for photothermal or other near-IR light-triggered therapy, while simultaneously providing increased T₁ contrast in MR imaging by concentrating Gd(III) within the nanoparticle. Measurements of Gd-NM revealed a strongly enhanced T₁ relaxivity (r₁ ∼ 24 mM^-1⋅s^-1) even at 4.7 T, substantially surpassing conventional Gd(III) chelating agents (r₁ ∼ 3 mM^-1⋅s^-1 at 4.7 T) currently in clinical use. By varying the thickness of the outer gold layer of the nanoparticle, we show that the observed relaxivities are consistent with Solomon-Bloembergen-Morgan (SBM) theory, which takes into account the longer-range interactions between the encapsulated Gd(III) and the protons of the H₂O molecules outside the nanoparticle. This nanoparticle complex and its MRI T₁-enhancing properties open the door for future studies on quantitative tracking of therapeutic nanoparticles in vivo, an essential step for optimizing light-induced, nanoparticle-based therapies.