Abstract
We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0 nm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1 mM−1s−1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors.
Highlights
Imaging techniques have developed exponentially during the past decades and many techniques, such as magnetic resonance (MR) imaging (Chen et al, 2014; Li et al, 2015b), computed tomography (CT) (Liu et al, 2012; Yin et al, 2013), radionuclide imaging (Nahrendorf et al, 2008; Guo et al, 2016), and ultrasound imaging (Lee et al, 2015), etc. have become indispensable in clinical use
The designed folic acid (FA)-Gd-Au PENPs were well characterized via different methods
After the formation of FA-Gd-Au PENPs, a peak appearing at 549 nm can be assigned to a surface plasmon resonance (SPR) peak of AuNPs. These results indicate that FA-Gd-Au PENPs have been successfully prepared
Summary
Imaging techniques have developed exponentially during the past decades and many techniques, such as magnetic resonance (MR) imaging (Chen et al, 2014; Li et al, 2015b), computed tomography (CT) (Liu et al, 2012; Yin et al, 2013), radionuclide imaging (Nahrendorf et al, 2008; Guo et al, 2016), and ultrasound imaging (Lee et al, 2015), etc. have become indispensable in clinical use. Nanoparticles (NPs) have been widely used in imaging techniques due to their unique electric, magnetic, and optical properties (Brigger et al, 2002; Laurent et al, 2008; Boisselier & Astruc, 2009). Polyethylene glycol (PEG)-derivatized phosphine oxide can be used to cap Fe2O3 NPs (size 1⁄4 3 nm) formed via thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. The generated small sized Fe2O3 NPs displayed a good biocompatibility and high r1 relaxivity of 4.78 mMÀ1sÀ1 and could be used for high-resolution T1weighted MR imaging of blood pool (Kim et al, 2011). Mesoporous silica NPs coated with AuNPs have been synthesized and used as a nanoprobe for ultrasound-induced cytoclasis, contrast-intensified ultrasound imaging, and ultrasound imaging-guided high intensity focused ultrasound surgical therapy (Wang et al, 2013)
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