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 lighttriggered 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 enhancementmechanism 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^-1s^-1) even at 4.7 T, substantially surpassing conventional Gd(III) chelating agents (r1 3 mM^-1s^-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 lightinduced, nanoparticle-based therapies.