Enhancing T ₁ magnetic resonance imaging contrast with internalized gadolinium(III) in a multilayer nanoparticle

Abstract

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 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 coresilica 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 T 1 contrast in MR imaging by concentrating Gd(III) within the nanoparticle. Measurements of Gd-NM revealed a strongly enhanced T 1 relaxivity (r 1 ∼ 24 mM

Molecular Imaging of Inflammation in Ischemic Heart Disease

“…As a result, there may be inaccurate identification and localization of inflammation using this technique. These limitations have led to the development of a number of positive contrast agents including extremely small supramagnetic iron oxide particles with a zwitterion coating that have high T1 constrast, 12 nonspecific and specific targeted gadolinium positive contrast agents, 13,14 and manganese contrast agents. 15 …”

Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units

“…Most clinically used contrast agents are based on paramagnetic (4f 7 ) gadolinium(III) ions, which interact with water molecules to improve the relaxation rates of the protons, enhancing the image contrast . The immobilisation of trivalent gadolinium units on the surface of gold nanoparticles dramatically increases the relaxation rate experienced by the protons of the water molecules in their vicinity . This can be partly traced to the effect on the rotational correlation time, which increases when the assembly rotates slowly, leading to greatly increased relaxivity per Gd 3+ ion.…”

“…This can be partly traced to the effect on the rotational correlation time, which increases when the assembly rotates slowly, leading to greatly increased relaxivity per Gd 3+ ion. In addition to this intrinsic enhancement, the presence of many gadolinium ions creates a multimeric effect on the relaxation of water protons due to the increased localised contrast agent concentration …”

“…[15] The immobilisation of trivalent gadolinium units on the surfaceo fg old nanoparticles dramatically increases the relaxation rate experienced by the protons of the water molecules in their vicinity. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] This can be partlyt raced to the effect on the rotational correlation time, which increases when the assembly rotatess lowly,l eading to greatly increased relaxivity per Gd 3 + ion. In addition to this intrinsic enhancement, the presence of many gadolinium ions createsamultimeric effect on the relaxation of water protons due to the increased localised contrasta gent concentration.…”

“…In addition to this intrinsic enhancement, the presence of many gadolinium ions createsamultimeric effect on the relaxation of water protons due to the increased localised contrasta gent concentration. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] All current clinicallya pproved gadolinium magnetic resonance contrast agents (such as Dotarem, showni nF igure 1a) are extracellularp robesw ith an on-specific biodistribution. One of the aims of the research described here is to add to the development of an ew generation of contrasta gents, which are able to recognise early reporterso fagiven pathology on the cellular surface.T he targetingo fo verexpressed membrane receptors using MRI is hampered by the very low concentration of such receptors and by the relatively low sensitivity of Gd 3 + contrast agents.…”