Investigation of the use of pyrrole doped amyloid based nanofibrous scaffold for skin cancer therapy

Worldwide, 19.3 million new cancer cases and 9.9 million cancer-related deaths were reported in 2020. Among these, 324,635 of these new cases and 57,043 of the deaths were melanoma cancer. Compared to previous years, the worldwide incidence of melanoma has increased gradually, and accounted for 75% of skin cancer-related deaths. Today, the methods used in the treatment of melanoma cancer depending on the stage of the disease are surgery, immunotherapy, chemotherapy, targeted therapy drugs, and radiation therapy. In an ideal cancer treatment, the primary goal is to preserve the integrity of the healthy tissue while the cancer cells are destroyed. During and after the treatment, it is not possible to eliminate cancer cells without damaging the healthy cells and regenerate the tissue. In accordance with this purpose, within the scope of the thesis, i) conversion of bovine serum albumin (BSA) to amyloid form (AL-BSA), ii) production of nanofibrous scaffolds in natural polymeric structure from AL-BSA doped with pyrrole in different mass ratios by using electrospinning method (Pd-AL- BSA), iii) physical and chemical characterization of AL-BSA and Pd-AL-BSA scaffolds, iv) in-vitro evaluation the effect of scaffolds on the healthy skin cells and melanoma cancer cells viability, and v) in-vitro antimicrobial property examination of scaffolds, studies have been carried out. Scanning electron microscopy, contact angle measurement, FTIR analysis, tensile test, and in-vitro hydrolytic and enzymatic degradation characterizations of AL-BSA, %5, %10, %20, and %50 Pd-AL-BSA scaffolds were performed. Cell and bacteria viability were followed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which is a colorimetric method. AL-BSA did not show any cytotoxic effect on BJ normal human skin cell and A375 human melanoma cell. Compared with AL-BSA, 50% Pd-AL-BSA scaffold increased BJ increased cell viability by 37.38 ± 2.39%, while A375 cell viability decreased by 64.27 ± 1.30%. Thus, whereas the viability of cancer cells is inhibited, the viability of healthy cells is increased. Compared to AL-BSA, 50% Pd-AL-BSA inhibited E. coli viability by 54.45 ± 2.85%, while it caused 51.28 ± 2.52% inhibition in S. aureus viability. AL-BSA showed anti-adhesive properties against E. coli and S. aureus compared to TCPS, while 50% Pd-AL-BSA showed antimicrobial activity. Consequently, it has been shown that 50% Pd-AL-BSA scaffold kills cancer cells while increasing the proliferation of healthy cells and has antimicrobial properties. It is thought that the pyrrole doped amyloid based scaffold produced within the scope of this thesis will shed light on the designs of new biomaterials for the future.