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Document Type |
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Thesis |
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Document Title |
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IMPACT OF CHITOSAN NANOPARTICLES COATED DENDRITIC CELLS-BASED VACCINE AS CANCER IMMUNOTHERAPY فعالية الخلايا الشجرية المغلفة بجزيئات النانو شيتوزان كعلاج مناعي ضد السرطان |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Dendritic cells (DCs) are major contributors to generate an effective immune response due to their ability to present antigen to T cells. Tumor microenvironment (TME) impact crucial immune cells and impair their functions including dendritic cells. Lately, nanoparticles are wildly used in different medical applications as a drug-delivery system to overcome impaired immune cells. Therefore, this research aims to develop an effective antitumor DC-based vaccine through coating DCs with Chitosan-nanoparticles (CH-NPs). Using cytokines and lipopolysaccharide (LPS), undifferentiated mouse bone marrow progenitor cells were differentiated into mature DCs. The ionic gelation method was used to prepare CH-NP then coated stimulated DCs. MTT test assessed all formulations' cytotoxicity. To compare the antitumor effect of CH-NPs, DCs, and DCs-CH-NPs, mice were randomized into five groups and injected with vaccine formulations. Flow cytometry was used to analyze DCs and CD4+ T cell activations in blood and spleen tissue after immunization. Histological samples of the spleen and lymph nodes were taken. Our results show that co-stimulatory molecules CD80/CD86 and DC maturation marker CD83 were upregulated in vaccination DCs, maturing them. In addition, CD83, CD11c, and MHC-II were upregulated in blood and spleen samples in vivo. DC-CH-NPs vaccinated group had a higher mean percentage of 76.7±17.1 for CD83 expression in blood samples compared to DCs group (47.7±11.0), and CH-NPs group (37.7±8.6). Spleen samples also expressed DC markers, particularly CD83. However, the DC-CH-NPs vaccinated group had considerably more CD4+T cells (MFI= 26.1±2.3) than DCs (18.6±1.6) and CH-NPs (13.3±1.4). The current work concludes that DC-CH-NP vaccine formulation can induce an effective in vivo immune response. This data may provide important knowledge to develop an effective delivery system for antitumor vaccine.
Keywords: Dendritic cells, Vaccine, Nanoparticles, Chitosan, Tumor Microenvironment. |
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Supervisor |
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Dr. Alia ALDahlawi |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1445 AH
2023 AD |
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Added Date |
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Sunday, October 15, 2023 |
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Researchers
| نجلاء سهيل العتيبي | Alotaibi, Naglaa Suhail | Researcher | Master | |
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