TY - THES

T1 - Investigation of novel approaches for the treatment of head and neck cancer with cold atmospheric plasma

AU - Vochitu, Elena

PY - 2024

Y1 - 2024

N2 - Head and neck squamous cell carcinoma (HNSCC) is an umbrella term for cancers that develop in the mucosal epithelium in the head and neck area. Current treatment options include surgical tumour removal, radiotherapy, chemotherapy, targeted therapy or immunotherapy. There is an urgent need for more effective treatments that enhance therapeutic efficacy and functional outcomes. Cold atmospheric plasma (CAP) has undergone multiple trials for applications in the medical field, including cancer treatment. We investigated the co-treatment of CAP with chemotherapeutics and DNA damage response inhibitors (DDRi) in A253 and FaDu cell lines using proliferation and spheroid growth assays and immunofluorescence. Data suggests an enhanced anti-proliferative effect on HNSCC in both 2D and 3D cultures. Our results indicate a possible synergistic effect between the combination of CAP and cisplatin or DDRi. We then progressed to testing cisplatin-loaded hydrogels as plasmaactivated hydrogel therapy (PAHT). PAHT combines CAP with hydrogel material, which is made of sodium polyacrylate and poly(vinyl alcohol). It can be loaded with cationic drugs such as cisplatin and, when exposed to CAP, the hydrogel changes in ionic strength and pH, leading to the delivery of the drug deep into the tissue. The antiproliferative effects of PAHT were measured using a cell proliferation assay and the results demonstrate that the combination led to enhanced cell death, although leakage of cisplatin from the gels in the absence of CAP was also noticed. This study demonstrates that CAP enhances the anti-proliferative effects of cisplatin and DDRi through both direct application and indirect PAHT treatment, emphasizing its potential to develop innovative therapies for HNSCC and highlighting PAHT's ability to aid in the locoregional treatment of this cancer.

AB - Head and neck squamous cell carcinoma (HNSCC) is an umbrella term for cancers that develop in the mucosal epithelium in the head and neck area. Current treatment options include surgical tumour removal, radiotherapy, chemotherapy, targeted therapy or immunotherapy. There is an urgent need for more effective treatments that enhance therapeutic efficacy and functional outcomes. Cold atmospheric plasma (CAP) has undergone multiple trials for applications in the medical field, including cancer treatment. We investigated the co-treatment of CAP with chemotherapeutics and DNA damage response inhibitors (DDRi) in A253 and FaDu cell lines using proliferation and spheroid growth assays and immunofluorescence. Data suggests an enhanced anti-proliferative effect on HNSCC in both 2D and 3D cultures. Our results indicate a possible synergistic effect between the combination of CAP and cisplatin or DDRi. We then progressed to testing cisplatin-loaded hydrogels as plasmaactivated hydrogel therapy (PAHT). PAHT combines CAP with hydrogel material, which is made of sodium polyacrylate and poly(vinyl alcohol). It can be loaded with cationic drugs such as cisplatin and, when exposed to CAP, the hydrogel changes in ionic strength and pH, leading to the delivery of the drug deep into the tissue. The antiproliferative effects of PAHT were measured using a cell proliferation assay and the results demonstrate that the combination led to enhanced cell death, although leakage of cisplatin from the gels in the absence of CAP was also noticed. This study demonstrates that CAP enhances the anti-proliferative effects of cisplatin and DDRi through both direct application and indirect PAHT treatment, emphasizing its potential to develop innovative therapies for HNSCC and highlighting PAHT's ability to aid in the locoregional treatment of this cancer.

U2 - 10.17635/lancaster/thesis/2793

DO - 10.17635/lancaster/thesis/2793

M3 - Master's Thesis

PB - Lancaster University

ER -