Drug-loaded nanobots for transmucosal delivery to mucinous tumours

Mucus is a defensive barrier that protects the underlying cells from pathogens and toxic compounds, although it also hinders the delivery of drugs whenever they are administered locally. There are different types of mucus-secreting tumours, such as pseudomyxoma peritonei (PMP), that could benefit from more efficient transmucosal delivery of anti-cancer drugs. PMP is a rare disease and the most mucinous tumour type, thus it will be used as a proof of concept for this project. In fact, it is characterised by the production of abundant mucus in the peritoneal cavity and is treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, usually Mitomycin C. This approach has extended patient survival, but there is a significant proportion of recurrence, most probably due to the shielding effect of mucus. Therefore, there is an urgent need to offer new therapeutic strategies to PMP patients. Recently, Dr. Palmer’s lab has established a collection of PMP patient-derived organoids and xenografts and has shown that some PMP patients present oncogenic BRAFV600E mutations, introducing a new druggable targeted mutation. In this proposal, Dr. Sánchez’s lab (IBEC), in collaboration with Dr. Palmer’s research group (VHIO), aims to use nanobots able to overcome the mucus barrier that will be loaded with Mitomycin C or Encorafenib (BRAF inhibitor) to treat PMP. A comparative study will be performed to assess the treatment’s efficacy compared to the standard of care, and medical advice will be received from Dr. Élez (VHUH) to ensure the translation of the results to the clinic. We believe that using this all-in-one system will certainly enhance the delivery and efficacy of the active therapeutic compound, thus potentially improving current treatments.