Genotoxic effects of a novel form of Gold Nanoparticles loaded with Hesperidin on head and neck cancer lymphocytes compared to effects from healthy control lymphocytes and Squamous cell Carcinoma of Maxillary sinus

The head and neck cancers (HNC) are a group of cancers that begin in the squamous cells that line the mucosal surfaces of the head and neck. Therefore, they are commonly known as squamous cell carcinoma of the head and neck. Squamous cell carcinoma of the maxillary sinus (MC) is a rare type of HNC, and it is a very aggressive tumour. This cancer is typically diagnosed at a very advanced stage and most patients have a poor survival rate and prognosis. This study is based on the synthesis and applications of gold nanoparticles (AuNPs) conjugated with hesperidin (Hsp) as a targeted drug delivery system. AuNPs are ideal for loading different drugs and delivering them to targets sites due to their stability, small size, substantial surface area, non-cytotoxic and inert nature. Hsp is a naturally occurring substance with anti-inflammatory and antioxidant capabilities. The main aim of this research was to develop a highly efficient and safer method to deliver Hsp to the target sites. The Hsp with poor solubility and bioavailability render it only slightly absorbed, requiring a delivery system to reach its therapeutic target. This study focused on the effects of 15μg/ml Hsp loaded on gold nanoparticles (Hsp-AuNPs) on 20 healthy individuals’ lymphocytes as compared to 20 HNC patients’ lymphocytes using the alkaline Comet assay. While enzyme-based Comet repair was performed on 5 healthy individuals’ lymphocytes as compared to 5 HNC patients’ lymphocytes. The Hsp-AuNPs reduced the DNA damage in HNC patients’ lymphocytes compared to the healthy lymphocytes (***p<0.001). Furthermore, the 15μg/ml of Hsp-AuNPs significantly reduced the oxidative stress caused by H2O2 and appeared to be effective in both groups using the Comet and Comet repair assay. Results from Comet and Comet repair assay were consistent. The human squamous cells of maxillary sinus (MC) were also treated with 5μg/ml of Hsp-AuNPs. The alkaline Comet assay results showed that Hsp-AuNPs induced DNA damage in MC cells (***p<0.001). Therefore, Hsp-AuNPs demonstrated the most substantial genotoxic effects and confirmed a possible anticancer agent. The Hsp was also used to treat lymphocytes from healthy individuals as compared to HNC patients’ lymphocytes they reduced the DNA damage, but they were less effective as compared to Hsp-AuNPs. Published data shows that using the AuNPs as a drug carrier has a more potent therapeutic effect against different diseases including cancer. Also, this study investigated the gene protective and genotoxic impact of bulk Hsp in Maxillary sinus carcinoma cells. The data obtained indicated that Hsp-AuNPs might possibly be effective for the treatment of MC and demonstrated the ability of Hsp-AuNPs to increase the DNA damage more than the bulk form of Hsp (***p<0.001). The outcomes of this study are consistent with the viewpoint that the Hsp-AuNPs might have a substantial role in cancer treatment, including MC. The concentration of 5μg/ml Hsp-AuNPs was used to treat the MC cells in Western blotting, and real-time polymerase chain reaction (qPCR) was based on a preliminary test for the optimal dose. The data obtained indicated that Hsp-AuNPs might potentially be effective for the treatment of HNC and showed the ability of Hsp-AuNPs to reduce DNA damage more than the bulk form of Hsp. Hsp-AuNPs has also shown anti-cancer potential in the MC cells by up-regulating the expression of p53, p21, PPAR gamma, and Caspase 3, at mRNA and protein levels by up-regulating the p53, PPAR gamma, Caspase 3, and p21 to mediate apoptosis and DNA repair in MC cells. The findings of this study are consistent with the view that the Hsp-AuNPs could have a significant role in cancer treatment, including HNC and MC.

URI

http://hdl.handle.net/10454/20206

Type

Thesis

Qualification name

PhD