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

癌症在欧洲是一个巨大的社会挑战，尽管只有不到10%的人口得到庇护，但全球四分之一的病例在这里被诊断出来。SMARTNANO将通过增加对这种疾病的了解，特别是对最具侵袭性的胰腺癌，更具体地说是对其肿瘤微环境（TME）的了解，帮助实现HorizonEurope的抗癌使命。因此，申请人将在优化治疗和加速药物转化方面尽自己的一份力量。胰腺导管腺癌（PDAC）是一种高度异质性肿瘤，具有非癌细胞的复杂微环境（基质）和富含酶（如金属蛋白酶（MMP））的细胞外基质。其特征还在于缺乏血管形成，导致严重缺氧，这有助于癌症的干性和血管生成。导致化疗/放疗效率低、癌细胞耐药、免疫逃避和转移。SMARTNANO旨在通过采用基于活性蛋白的纳米颗粒（ProNC）克服PDAC治疗的现有局限性，该纳米颗粒同时缓解缺氧并以受控方式递送基质重编程化合物，利用来自TME的金属蛋白酶。因此，癌细胞将更容易受到常规化疗和自身免疫系统的消除。此外，SMARTNANO将开发第一个有价值的体外人体平台，用于PDAC治疗的临床前研究，即密切模仿TME的性别分化类器官共培养。这个雄心勃勃的高风险，高回报的项目将促进申请人研究生涯的多学科性，帮助她成为未来的领导者，这要归功于精心设计的职业发展计划，其中她通过工程技术在肿瘤生物学和纳米颗粒合成方面的学习，与转移，领导力和知识保护方面的培训相结合。

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.