In silico design and validation of DNA-based aptamers targeting tumors using bacterial-mediated biotherapies

Bacteria-mediated biotherapy, also known as bacterial therapy or bacteriotherapy, is a treatment that utilizes live bacteria or bacterial products to treat various medical conditions. Despite their extensive exploration for treating many cancer types, the limited therapeutic efficiency of bacterial-mediated biotherapies, mainly because they do not accumulate tumor-specifically after delivery, has hindered their widespread application. However, this work brings hope by exploring the potential of aptamers in cancer-targeted therapy. Aptamers, nucleotides with the ability to bind targets similarly to antibodies, were the focus of our study. We used computational modeling to understand the interaction mechanism between aptamers and the nucleolin protein, which is overexpressed on the surface of cancer cells. We hypothesize that the aptamers used in this research will show specific binding interactions with the nucleolin protein. The aptamer PDB files were obtained using Vfold2D and Vfold3D programs, and these structures were then docked onto the nucleolin protein. Our studies revealed that the ULF aptamer formed strong interactions with the nucleolin binding site, further validating our results. This will enhance our understanding of the binding mechanism of aptamer to the nucleolin protein. The predicted aptamers can manipulate bacterial behaviors by changing the bacterial surface and can be an effective tumor imaging tool or therapeutic agent against the disease.