Synthesis of organic-inorganic hybrids via a high-pressure-ramp process: the effect of inorganic nanoparticle loading on structural and photochromic properties.

Organic polymerization remains a limiting step in the preparation of organic-inorganic hybrid materials with a strong concentration of the inorganic component. In this work, a high-pressure-ramp process was applied to achieve pHEMA-TiO2 nanoparticulate solids with an unprecedentedly high concentration (12 mol l-1) of the inorganic component, which is four times higher than that obtained after radical polymerization induced thermally or by photons. The inorganic nanoparticles underwent morphological and structural changes with an increase of Ti concentration above 1.5 mol l-1: they slightly coarsen and crystallize into an anatase polymorph. The material possesses a strong photochromic response related to the electron-hole separation at the organic-inorganic interface and can store 1e- per 5 Ti atoms. The electron storage capacity of the titania nanoparticles decreases upon crystallization.

Effects of adenovirus-mediated SV5 fusogenic glycoprotein expression on tumor cells.

BACKGROUND: The fusogenic (F) membrane glycoprotein of the paramyxovirus SV5 allows virus to enter host cells and mediates fusion between neighboring cells, which leads to cell death. F glycoprotein is synthesized as an inactive precursor (F(0)) that is cleaved by cellular protease furine to form the active heterodimer F(1) + F(2). The active protein can induce syncytium formation in the absence of another integral glycoprotein (HN), a property that appears to be unique among paramyxoviruses. METHODOLOGY: We constructed a non-replicative adenovirus to express SV5 F protein in tumor cells, and its fusion capacity was analyzed by fluorescent and confocal microscopy. Cell viability and bystander effect were compared with the thymidine kinase/ganciclovir suicide gene therapy. The structure of F-expressing cells was studied using electron microscopy. RESULTS: F glycoprotein expression induced syncytium formation to a maximum at 72 h, after which syncytia progressively lost viability and detached. The cell membrane was disrupted while nuclear structure was preserved. Over-expression of SV5 F protein in tumor cells led to high cytotoxicity comparable with that associated with the thymidine kinase/ganciclovir. A potent bystander killing effect was detected until the ratio of F-transduced to non-transduced cells was 1 : 100. CONCLUSIONS: These results indicate that the fusogenic glycoprotein of the paramyxovirus SV5 could be used to eliminate tumor cells and may encourage studies aimed at modifying its selectivity and combining its expression with other cytotoxic strategies to improve their efficacy.

Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53 delivery enhances tumour regression in human pancreatic cancer.

BACKGROUND: Strategies based on the introduction of pro-drug activating enzymes or the restoration of tumour suppressor genes have been proposed as encouraging methods to improve the efficiency of treatments in pancreatic cancer. The in situ bioactivation of cyclophosphamide by cytochrome p450-2B1 and subsequent p53 delivery were examined. MATERIALS AND METHODS: NP-18 cell line derived from a human pancreatic adenocarcinoma was treated in vitro with a combination of the Adenovirus-CYP2B1/cyclophosphamide and adenoviral-mediated wt-p53 reintroduction. Cell viability and cytometric cell cycle profiles were analyzed to evaluate the sensitivity of NP-18 cells to this treatment. The efficiency of this combination was assessed in an in vivo model consisting of xenografts into the subcutaneous tissue of Balb/c mice by tumour growth, histological analysis and cell cycle determinations. RESULTS: Ad-CYP2B1/cyclophosphamide or Ad-p53 treatments led to a marked decrease in cell viability of NP-18 cells. Combination of both treatments elicited a higher loss of cell viability and marked increases in sub-G1 population in cell cycle profiles. Animals treated with the combination strategy showed a quick reduction of tumour volumes due to the bioactivation of cyclophosphamide by CYP2B1 and sustained growth inhibition throughout the period evaluated after p53 delivery. Only this group of animals presented statistically significant differences with respect to control and cyclophosphamide-treated groups (P < 0.05). CONCLUSIONS: These results indicate that in situ bioactivation of cyclophosphamide by CYP2B1 and the recognition of the damaged DNA by p53 increase tumour regressions and may be a promising therapy for solid tumour therapy in man.