Periodic Reporting for period 1 - CONFINES (Controlling Cell Fate through Smart Nanoheaters)
Reporting period: 2015-09-09 to 2017-09-08
In CONFINES project, the fellow proposed a breakthrough approach aiming at the designing a unique Wnt-targeted nanodevice able to switch on/off the canonical Wnt signaling. To achieve this ambitious goal, Wnt3a protein, typically serving as pathway activator, was conjugated to magnetic nanoparticles, combining targeting and magnetic properties in a unique nanovector (NanoWnt). NanoWnt was conceive to control the cell signaling by operating in a dual mode i) as an activator of the canonical Wnt pathway, when it is naturally inactive or ii) as a nanoheater able to kill by magnetic hyperthermia those cells where the pathway is aberrantly activated.
The overall objective of CONFINES were:
Objective 1- Synthesis of magnetic nanoparticles conjugated to Wnt proteins (NanoWnt)
Objective 2- Evaluation of NanoWnt bioactivity to control cell fate in vitro and in vivo
Objective 3)- Evaluation of NanoWnt capacity to induce targeted hyperthermia in vivo and in vitro
Once obtained the desired nanodevice, NanoWnt was tested in cultured cells (B16, Hela and Mesenchymal stem cells) and in the freshwater polyp Hydra vulgaris in order to assess biocompatibility and bioactivity. Interestingly, NanoWnt resulted to be a safe and efficient system for the delivery of Wnt proteins. In more detail NanoWnt was able to activate Wnt signaling as observed in reporter transgenic lines. An additional strategy, based on chitosan/MNP nanocapsules was adopted to force the activation of Wnt signaling in Hydra though the efficient delivery of a specific Wnt pathway agonist.
Besides scientific achievements, CONFINES project has trained the applicant in essential areas of nanoscience, particularly made him confident with the design, synthesis and characterization of nanoparticles. Moreover, he acquired synthetic procedures to obtain bioengineered nanomaterial extending the know how of the applicant toward new disciplines.
Noteworthy, beyond personal career improvement, CONFINES demonstrate that Marie Curie Actions may significantly contribute to implement projects with highly interdisciplinary nature, which undoubtedly gain a synergic knowledge by converging diverse fields of investigations.