Multicolor core/shell silicananoparticles for in vivo and ex vivo imaging

Abstract

Biocompatible highly bright silica nanoparticles were designed, prepared and tested in small living organisms for both in vivo and ex vivo imaging. The results that we report here demonstrate that they are suitable for optical imaging applications as a possible alternative to commercially available fluorescent materials including quantum dots. Moreover, the tunability of their photophysical properties, which was enhanced by the use of different dyes as doping agents, constitutes a very important added value in the field of medical diagnostics.

Targeted dual-color silica nanoparticles provide univocal identification of micrometastases in preclinical models of colorectal cancer

“…For this purpose, NOD/SCID mice were injected intrasplenically with the highly metastatic CRC cell line HCT-116 m. In this well-established model, 21-28 days after cell injection animals develop a pseudo-orthotopic primary tumor in the spleen and several secondary tumors into the liver 14 Within this time frame, we injected either control or CGIYRLRStargeted single-or dual-color SPNs into the caudal vein and let them circulate for increasing periods of time starting from 1 h. This choice was based on our recently published data, showing a peak in the fluorescence emission in different organs, including the liver, during the first hour after untargeted SPN injection and a subsequent decrease with time. 5 Consistently, we observed a good reduction of nonspecific fluorescence (ie, the signals of untargeted SPNs in target tissues, and/or of targeted SPNs in nontarget tissues) after 6 h, maintaining this optimal signal-to-background ratio even after 16-24 h. A very similar outcome was obtained with CGVYSLRS-SPNs (data not shown). Nontargeted contrast agents have the disadvantage of being quickly removed from the bloodstream, thus requiring analysis to be performed shortly after injection (usually in the period of just minutes).…”

“…Often, this does not enable precise quantifications or allow for repeated analyses. Conversely, we recently demonstrated that SPNs (including untargeted) persist in the bloodstream for up to 3 h. 5 The results of the experimental set-up described above suggest that clearance of untargeted nanoparticles is paralleled by specific accumulation of targeted SPNs that remains constant for longer periods (up to 24 h). The possibility of exploiting such a wide time frame for diagnostic imaging of hepatic micrometastases further supports translation into clinical applications.…”

“…Remarkably, both dyes showed increased fluorescence quantum yields (Table S1) as a consequence of entrapment in the rigid silica matrix; this prevents geometrical rearrangements of the excited state (that can lead to nonradiative processes) and segregates the dyes from possible quenchers, including molecular dioxygen. 5 Dual-color SPNs exhibit different fluorescence properties (Table S1) due to the energy transfer (90% efficiency) from Rhod to Cy5. This allows a large separation between emission and excitation wavelengths; as a consequence, when these SPNs are excited in the Rhod absorption band, Rhod fluorescence decreases to 10%, with a concomitant increase in Cy5 emission.…”

Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities

“…9,25 Covalent doping of the silica core with alkoxysilane derivatized dyes produces PluS NPs that are very bright, with luminescent properties that were exploited in several fields, 26 such as the development of chemosensors, 27,28 fluorescent photoswitchable NPs, 29 NPs for electrochemiluminescence applications, 30,31 in vivo FOI, 5,9 and targeted fluorescence imaging. 9,32 Our previous findings have documented efficient cell internalization and lack of cytotoxicity of PluS NPs in some in vitro and in vivo assays.…”

Nano-Technological Approaches to Improve the Efficiency of Bio-Assays

“…In reality, this apparently simple looking reaction system has to face several difficulties before an appreciable signal is received by the photo-detector to give an analysable dataset. With the rapid emergence of nanotechnology during last few decades, some of the critical problems have been solved [1][2][3][4][5]. However, a large number of unresolved issues still remain there.…”