SMARTNANO: Enzyme Sensitive Protein-Based Drug Nanocarriers (ProNCs) for Reprogramming of Pancreatic Ductal Adenocarcinoma (PDAC).

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Cancer is a huge societal challenge in Europe, as despite sheltering less than 10% of the population, a quarter of all cases worldwide are diagnosed here. SMARTNANO will help to fulfill HorizonEurope's mission against cancer by increasing knowledge about this disease, specifically about one of the most aggressive, pancreatic cancer, and more specifically about its tumor microenvironment (TME). Thus, the Applicant will do its bit in optimizing treatments and speeding up the translation of drugs. Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor with a complex microenvironment (stroma) of noncancerous cells and an extracellular matrix rich in enzymes such as metalloproteases (MMPs). It is also characterized by a lack of vascularization, resulting in severe hypoxia, which contributes to cancer stemness and angiogenesis. Altogether leads to low efficiency of chemo/radiotherapy, resistance of cancer cells, evasion of immune system and metastasis. SMARTNANO aims to overcome the existing limitation of PDAC therapy by employing active protein-based nanoparticles (ProNC) that simultaneously alleviate hypoxia and deliver stromal reprogramming compounds in a controlled manner, harnessing metalloproteases from the TME. Therefore, cancer cells will be more susceptible to conventional chemotherapy and elimination by own immune system. In addition, SMARTNANO will develop the first valuable in vitro human platform for preclinical studies of PDAC therapeutics, in terms of gender-differentiated organoid co-cultures that closely mimic the TME. This ambitious high-risk, high-reward project will promote the multidisciplinarity of the applicant's research career, helping her become a leader of the future, thanks to the carefully designed career development plan in which her learning in tumor biology and nanoparticle synthesis through engineering techniques, are mixed with training in transfer, leadership and intellectual protection.