Within this action, we have been able to:
1. Demonstrate a facile and well-controlled synthesis of defined NPs morphologies using biocompatible, biodegradable and stimuli-responsive polypeptides as building blocks, which can be useful as drug delivery systems in a myriad of biomedical applications. Our strategy is highly significant and brings a new perspective to biodegradable NPs one-pot production based on poly(amino acids), particularly but not exclusively for application in the healthcare sector. Furthermore, the ROS-responsiveness and disassembly of our nanoparticles (that we monitor in situ thanks to LTEM) provide them with the ability to trigger their functional output under diseased/malfunctioning sites linked to mitochondria dysfunction. This is especially relevant in many pathologies including atherosclerosis, neurodegeneration, arthritis, diabetes, inflammation, cancer and metastasis where ROS is overproduced.
2.We followed a screening approach in which poorly water-soluble drugs are encapsulated in NPs to enhance drug solubility and facilitate intracellular delivery. By using a human pediatric glioma cell model, we demonstrated that our NPs mediated intracellular delivery of anticancer drugs. Additionally, when delivered in combination, drug-loaded NPs triggered both an enhanced drug efficacy and synergy compared to single drugs combinations. This is particular relevant since this versatile strategy can be further extended to other drug combinations to find new and effective synergistic drug combinations against paediatric glioma.
3.We have in deep investigated the mechanisms of transport across the BBB to the brain. To this aim we have used NPs with tunable amounts of ligands to a receptor present in the BBB used for transferring molecules from the blood to the brain side. We have elucidated the role of key actors (proteins) on the transport, and our findings show how depending on the amount of ligands used we can biase toward internalization in the cells and fast degradation and therefore no shuttling across, or a fast shuttling across the BBB. This is particularly relevant for the design of NPs to deliver drugs inside the brain for tumor treatments.
The work have been disseminated in several conferences as posters or oral presentations, including the well-known international ones: GRS and GRC Cancer nanotechnology conferences, Boston, 2019, ACS Fall San Diego, 2019, CRS Valencia Spain, 2019
This work has been also published in repositories (bioRxiv, ChemRxiv) and published in peer-reviewed journals. Although there are still some more publications coming after the end of the action, so far we have reported 8 publications.
All publications have been disseminated in social media (particularly Twitter) to help in their visibility.
