Gadolinium‐Doped Silica Nanoparticles Encapsulating Indocyanine Green for Near Infrared and Magnetic Resonance Imaging

Abstract

Clinical applications of the indocyanine green (ICG) dye, the only near infrared (NIR) imaging dye approved by the Food and Drug Administration (FDA) in the USA, are limited due to rapid protein binding, fast clearance, and instability in physiologically relevant conditions. Encapsulating ICG in silica particles can enhance its photostability, minimize photobleaching, increase the signal-to-noise (S/N) ratio and enable in vivo studies. Furthermore, a combined magnetic resonance (MR) and NIR imaging particulate can integrate the advantage of high-resolution 3D anatomical imaging with high-sensitivity deep-tissue in-vivo fluorescent imaging. In this report, a novel synthesis technique that can achieve these goals is presented. A reverse-microemulsion-based synthesis protocol is employed to produce 25 nm ICG-doped silica nanoparticles (NPs). The encapsulation of ICG is achieved by manipulating coulombic attractions with bivalent ions and aminated silanes and carrying out silica synthesis in salt-catalyzed, mildly basic pH conditions using dioctyl sulfosuccinate (AOT)/heptane/water microemulsion system. Furthermore, paramagnetic properties are imparted by chelating paramagnetic Gd to the ICG-doped silica NPs. Aqueous ICG-dye-doped silica NPs show increased photostability (over a week) and minimal photobleaching as compared to the dye alone. The MR and optical imaging capabilities of these particles are demonstrated through phantom, in vitro and in vivo experiments. The described particles have the potential to act as theranostic agents by combining photodynamic therapy through the absorption of NIR irradiated light.

Organic–inorganic nanohybrids for fluorescence, photoacoustic and Raman bioimaging

“…The use of indocyanine (ICG)-loaded hybrid SiNPs for in vitro and in vivo fluorescence imaging was explored by Sharma et al [23]. ICG is known for its instability in physiological conditions, and therefore, its encapsulation inside SiNPs preserves both its stability and photophysical properties.…”

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

“…The main multimodal strategies are superparamagnetic iron oxide and gadolinium MR contrast conjugated with NIRF dyes or NPs. 16,[92][93][94] Covalent binding of Fe 3 O 4 and different NIR dyes, such as Cy5 and QDs, has been extensively reported. [95][96][97] Xi et al combined NIR dye-labeled magnetic iron oxide NPs with a targeting moiety for urokinase plasminogen activator receptor (uPAR).…”

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

“…Mice were euthanized by inhalation of compressed CO 2 gas at various times (15,30, and 60 minutes) following injection with PEG-coated ICG-NCs, uncoated ICG-NCs, or freely dissolved ICG. Five mice were studied for each of the imaging agents and each time point, giving a total of 45 animals.…”

“…Such binding results in rapid clearance of ICG from blood (with plasma half-life in the order of 2-4 minutes). 26 We 7-11 and others [27][28][29][30] are pursuing encapsulation of ICG as a potential approach to increase its circulation time with the intention of broadening the medical applications of this clinically proven optical material.…”