الفهرس 
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Abstract
Squamous cells, basal cells, and monocytes are three types of cells found in the skin, the human body’s largest organ. Three kinds of SKCa, BCC, SCC, and melanoma, typically occur in the epidermis. The incidence of cancer is rising in both industrialized and developing nations, making it one of the major causes of death globally. Due to the intimate relationship between lifestyle variables and cancer, cancer prevention may be both more effective and less expensive. Natural remedies have been utilized to cure a variety of illnesses, and they are now a significant focus of drug development research. Numerous mechanisms, including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis, are modulated by these products, notably phytochemicals, which have received significant research and have proven to have anti-carcinogenic properties. The majority of effective anti-cancer medications already on the market are phytochemicals or their equivalents, and some are even being tested on humans. Micro-photodynamic therapy (MPDT) is a breakthrough and a modern technology to eliminate tumors and affected tissues without affecting the healthy tissue adjacent to and away from the tumor. This requires the use of a so-called photo-microsenstiser, which is highly concentrated in the tumor area, which responds ideally to photonic energy and microwaves, which works to stop tumor growth and elimination, which is a promising technique to eliminate superficial and deep cancer tumors.
The present work aimed to study microwave-assisted drug delivery of titanium dioxide / rose bengal chitosan-based nanoparticle for micro-photodynamic skin cancer treatment in vitro and in vivo. IRL and MW were used as energy sources.
In the current study, a total of 90 male Swiss albino mice, aged 60–65 days and weighing 205 gm. These mice and the human skin cancer cell line were used. Only after skin cancer was induced with (25 μg DMBA / 1 % Croton oil / 0.1 ml acetone/mouse) the treatment trial launched. The Medical Research Institute at Alexandria University’s ethical criteria was followed when using experimental animals in the study methodology.
In vitro study groups were as follows; group I: As an untreated control, a skin cancer cell line was kept in an environment free of drugs. group 1I: Skin cancer cell line was treated with titanium dioxide / rose bengal chitosan-based nanoparticles (TiO2/RB-CS) only. group III: Skin cancer cell line was exposed to Laser, for 3 min. group IV: Skin cancer cell line was treated with TiO2/RB-CS and exposed to laser for 3 min. group V: Skin cancer cell line was exposed to microwaves for 3 min. group VI: Skin cancer cell line was treated with TiO2/RB-CS and exposed to microwaves for 3 min. group VII: Skin cancer cell line was exposed to laser and microwaves for 3 min. group VIII: Skin cancer cell line was treated with TiO2/RB-CS, exposed laser, and microwaves for 3 min.
In vivo study groups were as follows; group I: 10 mice received topical administration of acetone for eight weeks, twice weekly as a vehicle only, and were kept without treatment and served as negative control. group 1I: 10 mice received topical administration of DMBA/ acetone for eight weeks, twice weekly, then one week after the initiation with DMBA, croton oil/ acetone was applied twice weekly for eight weeks for inducing skin cancer and did not receive any treatment and served as positive control. group III: 10 mice were subjected to the same condition of group II and treated daily with (TiO2/RB-CS) only for two weeks. group IV: 10 mice were subjected to the same condition of group II and exposed to the
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laser, for 3 min. for two weeks. group V: 10 mice were subjected to the same condition of group II and treated daily with (TiO2/RB-CS), The tumor site was exposed to laser at the same conditions of group IV for two weeks. group VI: 10 mice were subjected to the same condition of group II and exposed to microwaves, for 3 min. for two weeks. group VII: 10 mice were subjected to the same condition of group II and treated daily with (TiO2/RB-CS), then the tumor site was exposed to microwaves at the same conditions of group VI for two weeks. group VIII: 10 mice were subjected to the same condition of group II and exposed to laser followed by microwave, for 3 min. for two weeks. group IX: 10 mice were subjected to the same conditions of group II and treated daily with (TiO2/RB-CS), then tumor site was irradiated to laser followed by microwaves at the same conditions of group VIII for two weeks.
The treatment effects evaluation:
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SRB cytotoxicity and cell viability were done to detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwaves on skin cancer cell line.
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Biochemical examinations were applied to detect serum levels of ALT, AST, urea, and creatinine to detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwaves on liver and kidney functions.
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Activities of some antioxidants were measured, namely, (GSH, GST, GR, GPx SOD, Cat, TAC) and (MDA) creatinine to detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwave on antioxidant system and oxidative stress.
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Molecular detection of P53, Caspase 3,9, Bax, Bcl2, TNFα, and VEGF gene expression using qRt-PCR to detect the effect of TiO2/RB-CS nanocomposite on skin cancer cell line creatinine to detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwave on pro and anti-apoptotic as well as necrosis and angiogenesis.
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Evaluating the histological modifications in the tumor tissues after various therapies using Hematoxylin and Eosin (H&E) stain using a light microscope to detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwaves on skin tissue.
Results of the study:
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TiO2/RB-CS photo-micro sensitizer nanocomposite only without activation has little effect.
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The effect of exposing the in vitro cell line and in vivo tumor to laser as a PDT therapy elevated in the presence of the TiO2/RB-CS nanocomposite than using laser alone.
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MW had a greater impact on the in vitro cell type and in vivo tumor than an IRL did. Similar differences were reported when using MW exposure alone or with the TiO2/RB-CS nanocomposite present, with the greatest impact encountered when using MW with the TiO2/RB-CS nanocomposite present.
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Employing microwaves had a greater impact on the in vitro cell line and in vivo tumor than did using laser. Similar differences happened whether using microwave exposure alone or when it was combined with the TiO2/RB-CS nanocomposite, with the combined use of the two having the greatest effects.
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Using laser and microwaves in combination with TiO2/RB-CS nanocomposite was more effective than using either laser or microwaves alone to treat the in vitro cell line and in vivo tumor.
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The levels of MDA were significantly higher in the mice carrying the skin tumor alone when compared to the control healthy animals.
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In the presence of TiO2/RB-CS nanocomposite, the combination of IRL photodynamic and MW microdynamic therapy drastically reduced MDA levels.
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All SKCa cancer mouse groups displayed decreased GSH, SOD, CAT, GR, GPx, GST, and TAC enzyme antioxidant activity when compared to the healthy control group. In the groups getting a combined PDT and MWDT treatment, the addition of the TiO2/RB-CS nanocomposite greatly boosted both the enzymatic and non-enzymatic antioxidant defenses.
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It was found that TiO2/RB-CS nanocomposite treatment improved blood creatinine and urea level which is a sign of renal protection. This further supports the significance of TiO2/RB-CS nanocomposite in protecting against renal toxicity. Additionally, TiO2/RB-CS nanocomposite therapy prevented elevation in serum levels of ALT and AST which is a sign of the compound’s hepatoprotective properties. This further supports the importance of TiO2/RB-CS nanocomposite in protecting against hepatotoxicity.
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Molecular detection of (P53, Caspase 3,9, Bax, and TNFα; positive) (Bcl2, and VEGF; negative) gene expression using qRt-PCR shows the effect of TiO2/RB-CS nanocomposite on the skin cancer cell and detect the effect of TiO2/RB-CS nanocomposite in combination with laser and/or microwaves on pro and anti-apoptotic as well as necrosis and angiogenesis.
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The histological analysis showed that none of the tumors from the group of mice with skin cancer showed necrosis and that all of the tumors contained highly aggressive cells. Compared to groups lacking TiO2/RB-CS nanocomposite as a photo-micro sensitizer, tumors removed from animals receiving therapy revealed appreciable areas of necrosis.
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Large foci of discrete necrosis zones were observed in the group of animals that received a combination of photodynamic and microdynamic therapy in the presence of TiO2/RB-CS nanocomposite.