Supercritical carbon dioxide (SCCO2) containing calcium propionate or magnesium bicarbonate was used to deacidify paper. In the experiment, to compare the effects of SCCO2 technology deacidification and immersion deacidification, two kinds of paper samples were chosen to do these two kinds of deaciditication tests respectively. And pH, alkali reserve and mechanical properties of paper samples were measured before and after these treatments. The experiments showed that the pH and alkaline reserve of paper samples treated with SCCO2 were nearly similar to that of immersion treatments. Otherwise, compared with immersion deacidification, supercritical carbon dioxide had some advantages of strengthening the mechanical properties of paper and shortening treatment time.
Aim
Angiogenesis plays a major role in atherosclerotic plaque development and instability. Our study aims to develop a novel optical and magnetic resonance (MR) dual-modality molecular imaging probe to early detect unstable plaques in vivo by targeting biomarkers of angiogenesis in murine models of atherosclerosis (AS).
Methods
Immunofluorescence and western blot were used to detect the expression of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in activated Human Umbilical Vein Endothelial Cells (HUVECs). After synthesis and identification of novel short peptide VRBP1-targeted VEGFR2, HUVECs were co-cultured with FITC-VRBP1 to test specific affinity of VRBP1. Then VRBP1-UCNPstargeting VEGFR2 were constructed by conjugating VRBP1 to the surface of NaGdF4:Yb,Er@NaGdF4 nanoparticles. The characterization of the nanoparticles was performed by transmission electron microscopy (TEM), distribution of size, hydrodynamic size, zeta potential, absorption spectra, emission spectra, imaging intensity of different concentrations, binding affinity and cytotoxicity of nanoprobes in vitro. The upconversion luminescence (UCL) and MR imaging were performed to identify unstable atherosclerotic plaque in ApoE−/− mice in vivo and ex vivo. Morphological staining was used to verify AS model and angiogenesis, and Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) was used to confirm accumulation of the nanoparticles after imaging.
Results
After induced by hypoxia and ox-LDL, the expression of VEGFR2 in activated HUVECs was enhanced. FITC-VRBP1 can specifically bind to the HUVECs. Characterization of the nanoparticles showed that particles size is uniform with a stable structure, specific optical and MR signal, good binding affinity to VEGFR2 and low cytotoxicity. In vivo and ex vivo UCL imaging and quantitative analysis revealed that distinctive optical signal was observed in the regions of left carotid common arteries (LCCAs) of AS group after injection of VRBP1-UCNPs. Higher signal intensity on T1-weighted MR imaging appeared in the LCCA wall of AS group after injection. The results of morphological staining demonstrated angiogenesis in the atherosclerotic plaques, Gd ions in LCCAs, aortic arch and renal arteries bifurcations detected by ICP-AES confirmed accumulation of the nanoparticles in plaque.
Conclusions
We successfully design and synthesize a novel UCNPs using peptide VRBP1 targeting to VEGFR2. In vivo imaging demonstrates that VRBP1-UCNPs can be used to perform optical/MR dual-modality imaging targeting angiogenesis in plaques, which is a promising technique to early detect unstable atherosclerosis.
Atherosclerosis is the leading cause of vascular pathologies
and
acute cardiovascular events worldwide. Early theranostics of atherosclerotic
plaque formation is critical for the prevention of associated cardiovascular
complications. Osteopontin (OPN) expression in vascular smooth muscle
cells (VSMCs) has been reported as a promising molecular target for
the diagnosis and treatment of atherosclerotic plaques. The PPARδ
agonist GW1516 has been shown to inhibit VSMC migration and apoptosis.
However, GW1516 has low aqueous solubility and poor oral bioavailability,
which are major obstacles to its broad development and application.
In this study, GW1516@NP-OPN, which is anti-OPN-targeted and loaded
with the PPARδ agonist GW1516, was synthesized using a nanoprecipitation
method. The uptake of GW1516@NP-OPN was examined using fluorescence
microscopy and flow cytometry assay in VSMC in vitro models. Using
the Transwell assay and acridine orange/ethidium bromide staining
methods, we observed that the inhibition of VSMCS migration and apoptosis
was significantly higher in cells treated with GW1516@NP-OPN than
those treated with free GW1516. The western blot assay further confirmed
that GW1516@NP-OPN can increase FAK phosphorylation and TGF-βprotein
expression. The effect of NPs was further tested in vivo. The atherosclerotic
lesion areas were greatly decreased by GW1516@NP-OPN compared with
the free drug treatment in apolipoprotein E
–/–
mice models. Consequently, our results showed that GW1516@NP-OPN
stabilizes the PPARδ agonist aqueous formulation, improves its
anti-plaque formation activities in vivo and in vitro, and can therefore
be recommended for further development as a potential anti-atherosclerotic
nanotherapy.
In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(−) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.
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