Biodistribution studies of ultrasmall silicon nanoparticles and carbon dots in experimental rats and tumor mice

Abstract

Ultrasmall clearable nanoparticles possess enormous potential as cancer imaging agents. In particular, biocompatible silicon nanoparticles (Si NPs) and carbon quantum dots (CQDs) hold great potential in this regard. Their facile surface functionalization easily allows the introduction of different labels for in vivo imaging. However, to date, a thorough biodistribution study by in vivo positron emission tomography (PET) and a comparative study of Si vs. C particles of similar size are missing. In this contribution, ultrasmall (size <5 nm) Si NPs and CQDs were synthesized and characterized by high-resolution transmission electron microscopy (HR-TEM), Fourier-transform infrared (FTIR), absorption and steady-state emission spectroscopy. Subsequent functionalization of NPs with a near-infrared dye (Kodak-XS-670) or a radiolabel (64Cu) enabled a detailed in vitro and in vivo study of the particles. For radiolabeling experiments, the bifunctional chelating agent S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) was conjugated to the amino surface groups of the respective NPs. Efficient radiolabeling of NOTA-functionalized NPs with the positron emitter 64Cu was found. The biodistribution and PET studies showed a rapid renal clearance from the in vivo systems for both variants of the nanoparticles. Interestingly, the different derivatives investigated exhibited significant differences in the biodistribution and pharmacokinetic properties. This can mostly be attributed to different surface charge and hydrophilicity of the NPs, arising from the synthetic strategy used to prepare the particles.

Degradability and Clearance of Inorganic Nanoparticles for Biomedical Applications

“…injection. For instance, Licciardello et al reported that silicon nanoparticles and CDs with positively charged surface showed high uptake in the liver and intestine, probably owing to the production of a protein corona . Conversely, neutral or zwitterionic particles with little hepatic uptake were rapidly cleared through the urinary bladder by renal excretion.…”

Shedding light on gene therapy: Carbon dots for the minimally invasive image-guided delivery of plasmids and noncoding RNAs - A review

“…Recently, Licciardello et al [39] reported that the behaviour of CDs is dictated by their surface features. For example, with biocompatible PEG conjugates, gadolinium metallofullerene nanocrystalline (GFNCs)–CDs–PEG nanocarbon becomes highly stable in physiological environments and is excreted from the body in a reasonable period of time without obvious side effects [40].…”

Virus‐Like Particles as Theranostic Platforms

“…[ 156 ] Both CPMV and CCMV were tested in a wide variety of tissues, including the liver, spleen, bladder, and salivary glands, but showed no toxicity despite their broad biodistributions. [ 157 ] Unlike some synthetic NPs that remain in the body for weeks or even longer, [ 158,159 ] VLPs are subject to proteolytic degradation and are thus removed safely from the body within days. [ 115,129,160 ]…”