الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
Lung cancer is the most common cause of cancer death worldwide. Thereby, there is extreme importance of new treatment strategies as nanotechnology and targeting therapy with promising possibilities to control the aggressiveness of lung cancer. Dual CD44 and folate receptors targetable nanocapsule based on folic-polyethylene glycol-hyaluronic (FA-PEG-HA) were fabricated to improve the therapeutic activity of 4-Methylumbelliferone (4-MU) toward lung cancer. In this study, we fabricate 4-MU Nps as a hybrid polymeric (protamine) protein (albumin) nanocapsule with average size 300 nm in a spherical uniform, with average size 600 nm. The encapsulation efficacy was 96.15% of 4-MU total amount furthermore, 70.79% of drug released within the first 6 hours and the remaining was sustained released during 48 hours. The in vitro study of free 4-MU, 4-MU Nps and 4-MU@FA-PEG-HA Nps on A549 lung cancer cells reveal that the 4-MU Nps and 4-MU@FA-PEG-HA Nps were more cytotoxic than free 4-MU on A549 cells IC50 was significantly reduce from 224.5±1.46 in free 4-MU to be 119.67±0.85, and 64.75±1.54 μg/ml in treatment with 4-MU Nps and 4-MU@FA-PEG-HA Nps respectively. The staining of cells with
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acridine orang/ ethidium bromide (AO/EB) shows the apoptotic behavior of cancer cells. The observed therapeutic activity of 4-MU@FA-PEG-HA Nps on urethane-induced lung cancer model, potentiality revealed a tumor growth inhibitory effect via apoptotic mechanisms and angiogenesis inhibition. The results were supported by Enzyme-linked immunosorbent assay (ELISA) of transforming growth factors (TGFβ1) and serum HA, histopathological analysis as well as immunohistochemical staining of lung cancer specimens to study the expression of Ki67, CD44, Bcl-2 and caspace-3. Moreover, 4-MU@FA-PEG-HA Nps exhibited a promising safety profile. Hence, it is expected that our developed novel nano-system can be used for potential application on tumor therapy for lung cancer.