A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is a malignant tumor with a high incidence. The therapeutic effect of conventional chemotherapy and radiotherapy is not obvious. Photodynamic therapy (PDT) is an ideal modality to fight cancer, and the nature of photosensitizer limits its application in clinical therapy. The aim of this study was to explore a novel mode of drug delivery for the intervention of bile duct cancer. METHODS: Oxaliplatin and photosensitizer HCE6 were loaded with mesoporous silica nanoparticles (MSNs) to synthesize Oxaliplatin/HCE6-MSNs (OH-MSNs); the structure of OH-MSNs was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), the drug release rate was detected by high performance liquid chromatography; the cellular activity, apoptosis level, and the expression levels of intracellular apoptosis and autophagy-related factors of OH-MSNs on cholangiocarcinoma cells were observed by CCK-8, flow cytometry, colony formation assay, and Western blot; the effects of OH-MSNs on cholangioma growth were observed by mouse tumor formation, immunohistochemistry, and tissue Tunel staining. RESULTS: The release of OH-MSNs to Oxaliplatin was enhanced under acidic conditions; compared with Oxaliplatin or O-MSNs, OH-MSNs showed more potent killing effects against cholangiocarcinoma cells (P<0.05), and exerted notably inhibitory effects on the activity of cholangiocarcinoma cells (P<0.05), promoted their apoptosis (P<0.05), and greatly facilitated the expression of pro-apoptotic factors and autophagic factors in cholangiocarcinoma cells (P<0.05), and markedly inhibited the expression of anti-apoptotic factors and autophagic inhibitory factors (P<0.05); moreover, OH-MSNs could significantly suppress the growth of mouse cholangiocarcinoma (P<0.05) and induce apoptosis of tumor cells compared with Oxaliplatin or O-MSNs (P<0.05). CONCLUSION: MSNs loading greatly increases the killing effect of Oxaliplatin on cholangiocarcinoma cells and upgrades the autophagic level of cholangiocarcinoma cells, while OH-MSNs synthesized by further loading HCE6 have a more apparent killing effect on cholangiocarcinoma cells.

miR-203 Inhibits the Invasion and EMT of Gastric Cancer Cells by Directly Targeting Annexin A4.

Many studies have shown that downregulated miR-203 level is in a variety of cancers including gastric cancer (GC). However, the precise molecule mechanisms of miR-203 in GC have not been well clarified. In the current study, we investigated the biological functions and molecular mechanisms of miR-203 in GC cell lines. We found that miR-203 is downregulated in GC tissues and cell lines. Moreover, the low level of miR-203 was associated with increased expression of annexin A4 in GC tissues and cell lines. The invasion and EMT of GC cells were suppressed by overexpression of miR-203. However, downregulation of miR-203 promoted invasion and EMT of GC cells. Bioinformatics analysis predicted that annexin A4 was a potential target gene of miR-203. Next, luciferase reporter assay confirmed that miR-203 could directly target annexin A4. Consistent with the effect of miR-203, downregulation of annexin A4 by siRNA inhibited the invasion and EMT of GC cells. Introduction of annexin A4 in GC cells partially blocked the effects of miR-203 mimic. Introduction of miR-203 directly targeted annexin A4 to inhibit the invasion and EMT of GC cells. Overall, reactivation of the miR-203/annexin A4 axis may represent a new strategy for overcoming metastasis of GC.

Mir-196a-2 C>T polymorphism as a susceptibility factor for colorectal cancer.

OBJECTIVE: This study aimed to gain a better insight into the impact of the mir-196a-2 C>T polymorphism on the susceptibility to colorectal cancer (CRC). METHODS: In a meta-analysis of 6 publications with a total of 1,754 cancer cases and 2,430 controls, we summarized the data on the associations between the studied mir-196a-2 C>T polymorphism and CRC risk and conducted subgroup analyses by ethnicity and control sources. RESULTS: We found no overall association between the mir-196a-2 C>T polymorphism and CRC risk. But a significant association was found in the stratified analysis according to ethnicity among Asians (ORCC vs. TT = 1.22, 95% CI = 1.02-1.45, P heterogeneity = 0.718; ORCC vs. TC + TT = 1.22, 95% CI = 1.04-1.44, P heterogeneity = 0.590; ORallele C vs. allele T = 1.10, 95% CI = 1.01-1.20, P heterogeneity = 0.726) rather than Caucasians. CONCLUSIONS: Our results suggested that there was no overall risk of CRC in relation to the mir-196a-2 C>T polymorphism. However, this polymorphism was associated with an increased risk in Asian populations.

"Green" functionalization of magnetic nanoparticles via tea polyphenol for magnetic resonance/fluorescent dual-imaging.

Tea polyphenol serves as an environmentally friendly ligand-exchange molecule to synthesize multifunctional metal-doped superparamagnetic iron oxide nanoparticles via a catechol-metal coordination interaction. The resultant particles not only exhibit excellent hydrophilicity and protein adsorption resistance, but also are applicable as magnetic resonance/fluorescent dual-imaging probes due to their high T2 relaxivity, autofluorescence and large cellular uptake.

Synthesis of superparamagnetic Fe3O4/PMMA/SiO2 nanorattles with periodic mesoporous shell for lysozyme adsorption.

A new kind of nanorattle, composed of a Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospherical core and mesoporous SiO(2) shell, has been successfully synthesized with the combination of a modified stöber method and a dual-template strategy, followed by alcohol dialysis. The nanorattles showed high efficiency in protein adsorption and separation.

Controllable preparation of ternary superparamagnetic nanoparticles dual-doped with Mn and Zn elements.

Superparamagnetic iron oxide nanoparticles (SPIONs) with high saturation magnetization are successfully synthesized via thermal decomposition method by doping Mn and Zn elements simultaneously. The synthesis procedure was modified according to the thermal stabilities of the precursors, in order to ensure that the stoichiometry of the synthesized samples can be retained exactly from the starting ratios of the Fe/Mn/Zn in the initial precursors. As a result, the saturation magnetization of the dual-doped nanoparticles increased about 23% compared to that without the dopants. The superparamagnetic nanoparticles had narrow size distribution and the average diameter was about 8 nm. XRD and HRTEM analyses also indicated that the materials had a cubic spinel structure.

Facile synthesis of monodisperse superparamagnetic Fe3O4/PMMA composite nanospheres with high magnetization.

Monodisperse superparamagnetic Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospheres with high saturation magnetization were successfully prepared by a facile novel miniemulsion polymerization method. The ferrofluid, MMA monomer and surfactants were co-sonicated and emulsified to form stable miniemulsion for polymerization. The samples were characterized by DLS, TEM, FTIR, XRD, TGA and VSM. The diameter of the Fe(3)O(4)/PMMA composite nanospheres by DLS was close to 90 nm with corresponding polydispersity index (PDI) as small as 0.099, which indicated that the nanospheres have excellent homogeneity in aqueous medium. The TEM results implied that the Fe(3)O(4)/PMMA composite nanospheres had a perfect core-shell structure with about 3 nm thin PMMA shells, and the core was composed of many homogeneous and closely packed Fe(3)O(4) nanoparticles. VSM and TGA showed that the Fe(3)O(4)/PMMA composite nanospheres with at least 65% high magnetite content were superparamagnetic, and the saturation magnetization was as high as around 39 emu g(-1) (total mass), which was only decreased by 17% compared with the initial bare Fe(3)O(4) nanoparticles.