Controlling Cell Fate through Smart Nanoheaters

Información del proyecto

CONFINES

Identificador del acuerdo de subvención: 657566

DOI

10.3030/657566

Proyecto finalizado el 19 Junio 2017

Fecha de la firma de la CE 23 Marzo 2015

Fecha de inicio 9 Septiembre 2015

Fecha de finalización 9 Septiembre 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 170 121,60

Aportación de la UE

€ 170 121,60

Coordinado por

UNIVERSIDAD DE ZARAGOZA
Spain

Periodic Reporting for period 1 - CONFINES (Controlling Cell Fate through Smart Nanoheaters)

Período documentado: 2015-09-09 hasta 2017-09-08

Resumen del contexto y de los objetivos generales del proyecto

The control of cellular processes is an important challenge to be addressed in cell biology and medicine. Over recent years, nanomaterial science has provided advanced engineered nanodevices which may establish a spatio-temporal control of cell fate through a tight modulation of molecular pathways activity. Wnt signalling is one of the most conserved pathway in animal kingdom providing important instructions for development and cell proliferation/differentiation. Additionally, activating or inactivating defects have been closely associated with developmental diseases and cancer. A multitude of studies have contributed to the elucidation of Wnt pathway components and their functions, opening a path to developing specific molecular strategies to modulate its state. A schematic illustration of the pathway and its functional activation is reported in Figure 1.
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

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

Since Dr. Alfredo Ambrosone (the fellow) moved to the University of Zaragoza, he opened up a new research line aiming at achieving the main objectives of CONFINES. NanoWnt was obtained through three distinct steps:1- Synthesis of Iron oxide Nanoparticles (MNPs); 2- Dye conjugation to add self-tracking features to the final device; 2- Wnt protein conjugation to the nanoparticle surface.
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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The results obtained in the frame of CONFINES project provided evidences that bridging the Wnt signaling to nanotechnology has great potential for developing new tools with therapeutic and diagnostic value. The main progress beyond the state of the art concerns the size of the nanodevice. So far, Wnt proteins have been linked only to micrometric supports which may pose severe limitations in terms of cell uptake. CONFINES achievements demonstrate that Wnt protein conjugation to nanoparticles result in smart nanodevices able to control Wnt signaling activation. This novel functional material, besides academic interest, may have the potential in a number of future applications in material science and nanomedicine. Taken into account the significant impact of this finding, deeper investigation on this topic are strongly demanded.
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.

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