Delivery of your payload into the cells
Since Nanofitins® do not passively internalize, the mechanism of action relies on a receptor-mediated intracellular uptake of the Nanofitin® and its payload. We are currently investigating the intracellular trafficking of our Nanofitins® and they seem to be devoid of lysosome addressing, which is the major degradation compartment in eukaryotic cells, allowing then the functional intracellular delivery of macrobiomolecules. We already demonstrated with different payloads (enzymes, ASO) intracellular activity of the payload when coupled to an internalizing Nanofitin®.
Intracellular activity of Nanofitins®
Thanks to the stability of their scaffold, Nanofitins® binding is conserved in the reducing intracellular environment, making them ideal candidates to address intracellular targets, both for targeting specific compartments into the cells or to use Nanofitins® as intracellular PPI inhibitors. This was notably demonstrated with the University of Bourgogne Franche-Comté on HSP110 (Marcion et al., Nanofitins targeting HSP110: An innovative immunotherapeutic modality in cancer, International Journal of Cancer 2021).