Ibrahim H. Borai

Photodynamic therapeutic activity of indocyanine green entrapped in polymeric nanoparticles.

BACKGROUND Photodynamic therapy (PDT) is a therapeutic modality involving the use of a photosensitizer agent activated by light of appropriate wavelength to selectively destroy tumor cells. Indocyanine green (ICG) is a promising photosensitive agent for PDT of tumor cells. The main disadvantage of using ICG in PDT is the instability of ICG in aqueous solutions. Encapsulating ICG dye in a biocompatible matrix based on PEBBLE technology showed an improvement of aqueous stability comparing with free ICG dye. The main objective of this study is to investigate the photodynamic effect of ICG-ormosil PEBBLEs on two different cell lines: human breast adenocarcinoma cells (MCF-7) and hepatocellular carcinoma cells (HepG2). METHODS ICG-embedded ormosil PEBBLEs were synthesized based on a sol-gel process, and characterized by transmission electron microscopy and other fluorescence tests. The cell viability was evaluated by MTT and trypan blue assays. Apoptosis, necrosis, and DNA damage (comet assay), were evaluated by fluorescence microscopic tests. RESULTS The results declared that ICG-ormosil PEBBLEs and free ICG both have the same cytotoxic and phototoxic effect on MCF-7 and HepG2 cell lines, where the apoptotic mode of cell death is preferentially occurred in case of PDT using ICG-ormosil PEBBLEs. Both ICG and ICG-ormosil PEBBLEs induced DNA damage after laser exposure. These results would suggest that entrapping ICG in Polymeric nanoparticles forming ICG-ormosil PEBBLEs improve the aqueous stability of the photosensitizer and in the same time retain its photodynamic activity, suggesting that it is preferred to use ICG-ormosil PEBBLEs instead of free ICG dye.

Photodynamic therapeutic effect of indocyanine green entrapped in polymeric nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice.

BACKGROUND Indocyanine green (ICG) is a promising photosensitive agent for photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the aqueous stability of the entrapped ICG molecules. The study objective is to investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate. METHODS Skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) followed by a PDT protocol for four weeks. RESULTS PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the inflammatory mediators tumor necrosis factor (TNF-α), nitric oxide (NO), cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR. CONCLUSION The present study indicated the effectiveness of PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size, apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to anti-EGFR was found to be more effective in inhibiting VEGF and in increasing caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT efficacy.

Effect of Gamma-Irradiation or/and Extrusion on the Nutritional Value of Soy Flour

Although soybean is rich with high amount of protein, phenolic compounds and other bioactive nutrients, their bioavailability and utilization by either humans or animals are relatively low due to the presence of high proportions of various antinutrients. Therefore, this study was assessed to use gamma irradiation or/and extrusion for inactivation or removal of certain antinutritional factors as well as study the effect of these processing method on the nutritional value of soy flour (the simplest form of soy protein). Analyses included proximate composition, the level of total phenols and levels of antinutrients (phytic acid, tannins and trypsin inhibitors) of raw and processed soy flour. In addition, amino acid contents were analyzed by using high performance amino acid analyzer-Biochrom 20, gas chromatography was used for analysis of fatty acids as well as phenolic compounds were determined by high performance liquid chromatography. The results showed that moisture, crude protein, crude fat, crude fiber, and ash were unchanged by the irradiation (5 and 10 KGy) or/and extrusion except the moisture content was decreased by extrusion. γ-irradiation or/and extrusion processing significantly reduced the levels of phytic acid, tannins, and trypsin inhibitor while the total phenols was increased relative to unprocessed control samples. All essential amino acids, fatty acids and phenolic compound were changed by different values. From these results, it could be possible to demonstrate the benefits of γ-irradiation or and extrusion processing on the nutritional properties of soy flour by reducing its antinutritional contents and improving some of functional nutrients.

The prophylactic and therapeutic effects of Momordica charantia methanol extract through controlling different hallmarks of the hepatocarcinogenesis

Inspite of the wide facilities for controlling cancer growth, there are little drugs to inhibit its metastasis or prevent its angiogenesis. Discovering such natural or synthetic multi-targeted agent that might strike different targets is considered as a vital goal for tumor controlling. In a previous study, the chemoprotective effect of methanol extract of Momordicacharantia (MEMC) on albino western rats bearing hepatocarcinogenesis was evaluated. The mechanism by which MEMC exert its anticancer properties was unknown. Therefore, we aimed in this study to investigate the possible role of MEMC as anti-proliferative, anti-angiogenic and anti-metastatic agent to exert its chemoprotective effect. The study was conducted on sixty albino western rats divided into six groups, 10 rats each. Diethylnitrosamine (DENA) was injected intraperitoneally (i.p.) at a dose of 200 mg/kg body weight once, 2 weeks later rats were received carbon tetrachloride (CCl4) subcutaneously (3 ml/kg/week) continued for 10 weeks. MEMC was orally produced to rats (40 mg/kg) alone, as well as before, at the same time and after DENA injection. Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), caspase-3,-8 (Casp-3,-8), histone deacetylase (HDAC) and matrixmetalloproteinases-2,-9 (MMP-2,-9) were evaluated. MEMC treatment significantly decreased Cox-2, VEGF, HDAC and MMP-2,-9 and increased Casp-3,-8 as compared to DENAgroup,which demonstrated that the anticancer effect of MEMC may be through the inhibition of angiogenesis, proliferation and metastasis and the activation of apoptosis. The improvement in before-treated group was more pronounced than that in after- and simultaneous-treated groups, indicating thatMEMC may act as a prophylactic agent more than being a therapeutic agent.

Therapeutic impact of grape leaves polyphenols on certain biochemical and neurological markers in AlCl3-induced Alzheimer’s disease

Alzheimers disease (AD) is a grave and prevailing neurodegenerative disease, characterized by slow and progressive neurodegeneration in different brain regions. Aluminum (Al) is a potent and widely distributed neurotoxic metal, implicated in the neuropathogenesis of AD. This study aimed to evaluate the possible neurorestorative potential of Vitis vinifera Leaves Polyphenolic (VLP) extract in alleviating aluminum chloride (AlCl3)-induced neurotoxicity in male rats. AlCl3 neurotoxicity induced a significant decrease in brain/serum acetylcholine (ACh) contents and serum dopamine (DA) levels, along with a significant increment of brain/serum acetylcholinesterase (AChE) activities. In addition, Al treatment resulted in significantly decreased serum levels of both total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF), and significantly increased serum levels of both interleukin-6 (IL-6) and total homocysteine (tHcy), as compared to control. Behavioral alterations, assessed by the T-maze test, showed impaired cognitive function. Furthermore, AD-brains revealed an increase in DNA fragmentation as evidenced by comet assay. AlCl3 induction also caused histopathological alterations in AD-brain. Treatment of AD-rats with VLP extract (100mg/kg body weight/day) improved neurobehavioral changes, as evidenced by the improvement in brain function, as well as, modulation of most biochemical markers, and confirmed by T-maze test, the histopathological study of the brain and comet assay. The current work indicates that the VLP extract has neuroprotective, antioxidative, anti-inflammatory, and anti-amnesic activities against AlCl3-induced cerebral damages and neurocognitive dysfunction.