Preparation of Silk Fibroin Nanofibers Containing 5-Fluorouracil for pH-Sensitive Drug Delivery and Synergistic Cancer Therapy
摘要
Every year, over one million instances of gastric carcinoma receive diagnoses on a global scale. The objective of the present study was to explore the synergistic impact of silk fibroin nanofibers (SFNFs) containing the pharmaceutical agent 5-fluorouracil (5-FU) in managing gastric cancer, centering on the MKN-45 cell line. For this study, we produced a nanofiber structure using a ratio of 1:5 of 5-FU to SFNFs. We analyzed the SFNFs using Fourier-transform infrared spectroscopy (FT-IR), UV spectroscopy, and scanning electron microscopy (SEM). The effect of pH on drug release was measured using the dialysis method. After this, assessments of cellular toxicity and the transcription of apoptotic (Bax, Bcl-2, and p53) and autophagic (Beclin-1 and LC3-II) genes were conducted utilizing MTT and PCR methodologies. In summary, SFNFs showed excellent controlled 5-FU delivery at different pHs and the amount of 5-FU release has increased as the pH decreases. Moreover, the merging of nanofibers with 5-FU substantially augmented the transcription of apoptosis and autophagy-associated genes, after 3 and 5 days (P-value < 0.05). It seems that the anticancer mechanism of 5-FU entails stimulating the expression of the mentioned genes, a process that can be facilitated by the presence of SFNFs.
Graphical Abstract