الفهرس 
MATERIALS AND METHODSOnly 14 pages are availabe for public view
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Abstract
Oral squamous cell carcinoma (OSCC) remains one of the most difficult malignancies to control because of its high ability for local invasion and metastasis. Despite the advances in therapeutic strategies (surgery followed by combined radiochemotherapy), the prognosis is still poor. The survival rates have not changed during the last 20 years, with high mortality rates.
Nanotechnology opens a new gate in cancer treatment, especially in the fields of drug delivery system. Nanoparticles for drug delivery system are available in different materials, sizes, and shapes. Of these nanoparticles, gold nanoparticles (AuNPs) have attracted the attention due to their unique physical, chemical, and optical properties.
The AuNPs need to be functionalized with surface ligands to be used as drug delivery system in vivo. For bio-distribution, polyethylene glycol (PEG) is used to avoid clearance of AuNPs by reticuloendothelial system. Meanwhile, the tri-peptide RGD is used to recognize the cancer cells through RGD-integrin interaction.
Gold NPs furthermore, due to its unique optical properties are used in cancer treatment as photothermal therapy (PTT). Illumination of the AuNPs with a beam of laser that is tunable to the appropriate wavelength results in conversion of the light energy to heat energy. The elevated temperature therefore, could induce apoptosis in the cancer.
The objective of the current study was to evaluate the therapeutic effect of PEG-RGD-AuNPs loaded with doxorubicin (DOX) chemotherapeutic agent as drug delivery system, together with the effect of AuNPs as PTT in the treatment of chemically induced OSCC in vivo. The citrate reduction method was used to prepare 30 nm AuNPs. Oral SCC was chemically induced by in the left buccal pouches of 112 golden Syrian hamsters.
After period of 6 months of cancer induction, the 98 remaining hamsters were divided into 4 main groups; control saline group, free DOX group,
Summary
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PEG-RGD-AuNPs group, and PEG-RGD-DOX-AuNPs group. The treatments were given by 2 routes; intraperitoneal (IP) and intralesional (IL). Further subdivision of these groups was made to be with laser and without laser subgroups.
The clinical evaluation of the proposed treatment was in terms of measuring the changes in the tumor volumes before and after treatment, and the survival rate. Both the greatest decrease in the tumor volume and the longest mean survival rate were shown in PEG-RGD-DOX-AuNPs IL-with- laser subgroup followed by IP-with-laser subgroup. Also, the subgroups (IP and IL) that were treated without laser in the PEG-RGD-DOX-AuNPs group revealed significant tumor volume decrease and significant increase in the survival rate, but to a lesser degree.
The histological assessment showed significant apoptotic index (AI) in the 4 subgroups of the PEG-RGD-DOX-AuNPs, with the highest AI recorded in IL-with-laser subgroup. Furthermore, the proliferative activity of this subgroup revealed the significant lowest mean area percent and mean optical density, followed by IL-without-laser subgroup, by using MCM3 proliferative immunhistochemical marker.