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.

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.