The treatment of liver injuries or hepatocellular carcinoma (HCC) with has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system (RES). As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic MRIactive contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MRI imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNPloaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP–loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.
The tridentate adsorbates cyclohexane-cis,cis-1,3,5-triyltrimethanethiol (CyTSH) and (cis,cis-1,3,5-trimethylcyclohexane-1,3,5-triyl)trimethanethiol (3C1CyTSH) were designed and synthesized. Thin films prepared by the adsorption of these molecules onto the surface of gold were characterized by ellipsometry, contact angle goniometry, polarization modulation infrared reflection absorption spectroscopy, and X-ray photoelectron spectroscopy (XPS). CyTSH was found to generate multilayer thin films with many unbound thiol species and oxidized sulfur moieties (e.g., disulfides and sulfones). In contrast, 3C1CyTSH was found to generate monolayer films in which ~90% of the thiols were bound to the surface of gold (~10% unbound), and there were no oxidized sulfur species. In comparing CyTSH and 3C1CyTSH, the methyl groups of 3C1CyTSH impart rigidity to the structure, which significantly enhances the chemisorption of sulfur to the surface of gold. Ellipsometric measurements and analysis by XPS indicate that the thickness of the self-assembled monolayer formed from 3C1CyTSH is ~5 Å.
Failure to remove a retrievable inferior vena cava (IVC) filter can cause severe complications with high treatment costs. Polydioxanone (PPDO) has been shown to be a good candidate material for resorbable IVC filters. However, PPDO is radioluscent under conventional imaging modalities. Thus, the positioning and integrity of these PPDO filters cannot be monitored by computed tomography (CT) or x-ray. Here we report the development of radiopaque PPDO IVC filters based on gold nanoparticles (AuNPs). Commercially available PPDO sutures were infused with AuNPs. Scanning electron microscopy analysis confirmed the presence of AuNP on the surface of PPDO. Micro-CT and x-ray images of the AuNP-infused PPDO sutures showed significant signal enhancement compared to untreated PPDO sutures. Elemental analysis showed that gold loading exceeded 2000 ppm. Tensile strength and in vitro cytotoxicity showed no significant difference between AuNP-infused and untreated PPDO. In a 10-week stability study, neither the gold content nor the radiopacity of the infused PPDO sutures significantly changed in the first 6 weeks. The increased attenuation of AuNP-infused PPDO sutures indicates their major advantage as a radiopaque resorbable filter material, as the radiopacity allows monitoring of the position and integrity of the filter, thereby increasing its safety and efficacy.
Tridentate cyclohexyl-based alkanethiolate SAMs generated from a series of adsorbates of the form R3C6H6(CH2SH)3, where R = -(CH2)nH and n = 3, 8, and 13 (3CnCyTSH), were examined. Characterization of the SAMs by X-ray photoelectron spectroscopy (XPS) revealed that all sulfur atoms of the tridentate adsorbates were bound to the surface of gold, and that the tailgroups were in general less densely packed than the SAM derived from octadecanethiol (C18SH). For each of the SAMs, the relative molecular coverage on the surface was estimated from the XPS-derived C1s/Au4f ratios. The trend in conformational order for these SAMs as determined by the surface interactions with contacting liquids and the relative crystallinity of the alkyl chains as revealed by the PM-IRRAS spectra were found to decrease as follows: C18SH >> 3C13CyTSH > 3C8CyTSH > 3C3CyTSH. A preliminary study of the thermal stability of the SAMs as evaluated by XPS indicates that the SAM generated from the cyclohexyl-based adsorbate with the longest alkyl chain, 3C13CyTSH, is markedly more stable than the SAM generated from C18SH. Overall, the results suggest that the stability of the SAMs are influenced by both the length of the alkyl chains and the chelate effect associated with the tridentate adsorbates.
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