Abstract
BackgroundIn this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly.ResultsOur ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS.ConclusionThese biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.
Highlights
In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform
We demonstrate here that the ultrasmall size of the nanoparticles conjugated with folic acid can take advantage of the folate receptor expressed at the blood–brain barrier (BBB) (Afzalipour et al 2019; Wu and Pardridge 1999) to facilitate the transport of the nanoparticles across BBB
The formation of ultrasmall β-NaGdF4:Yb50% nanoparticles is confirmed by its very broad X-ray diffraction patterns, which conform to the standard XRD peaks of the hexagonal β-phase N aGdF4 (JCPDS 27–0699) (Fig. 1d)
Summary
We report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. Relevant, multifunctional nanoparticles that combine diagnostic and therapeutic platforms are of high scientific interest, with significant societal impact (Chen et al.2016,2017; Dasgupta et al 2020). These theranostic nanomaterials often result in complex and large-sized structures to accommodate the various components that provide multi-functionality. Clearance through the kidneys occurs quickly, as the nanoparticles are filtered from the blood and excreted out This significantly reduces the risk of potential toxicity, which makes the renal clearance pathway an attractive route of elimination. This significantly reduces the risk of potential toxicity, which makes the renal clearance pathway an attractive route of elimination. (Du et al (2018)) glomerular filtration is strongly dependent on size, with a hydrodynamic diameter filtration-size threshold of < 6 nm. (Longmire et al 2008) the development of ultrasmall, biocompatible, multifunctional nanoparticles is of high interest for potential clinical use (Longmire et al 2008; Xie et al 2020; Choi et al 2010)
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