NANORESISTANCE · Management of Resistance to Tyrosine Kinase Inhibitors with Advanced Nanosystems

NANORESISTANCE introduces for the first time (i) receptor -independent targeting of Epidermal Growth Factor Receptor-kinase activity, (ii) nuclear delivery of anti-Epidermal Growth Factor Receptor therapy with novel grafting techniques and (iii) the deciphering of resistance and lack of responsiveness to anti-EGFR therapies in the preclinical setting with mathematical models of interstitial biodistribution. This work defines an unprecedented integrated approach for the comprehensive management of failure to anti-EGFR therapy and treatment monitoring. This partnership will play a structuring role by allowing researchers to acquire key skills equally relevant to the public and private sectors including cutting edge nanobiotechnology techniques for fabrication of nanotheranostic conjugates for targeted nuclear drug delivery and imaging, pioneering approaches for intracellular targeting with carbon nanotubes (CNT), innovative mathematical models and assessment of biodistribution, state-of-the-art Surface Plasmon Resonance for assessing drug-target interactions, emerging technologies for in vivo protein-protein and theranostic compound-protein interaction with Bimolecular Fluorescence Complementation Assays (BIFCs).These parallel approaches provide a promising innovative solution in the multifaceted challenge of the overall resistance to anti-EGFR therapies. This will be achieved with the development of multimodal CNT-based nanoplatforms carrying the fluorescent conjugates of EGFR inhibitors intracellularly independenly of EGFR extracellular recognition. This system will further deliver anti-EGFR and fluorescent attributes to the nucleus. The partnership offers and a well-structured scheme of complementary skills highly inspired by the entrepreneurial spirit of academicians and research commitment of the industrial partners securing significant impact on their employability in their sector.