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H2020Individual fellowship2015–2018

CONFINES · Controlling Cell Fate through Smart Nanoheaters

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-09-09 → 2018-09-09
EU contribution
€170,122
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

Controlling Cell Fate through Smart Nanoheaters

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

Data: CORDIS, © European Union

Project objective

Achieving the control of cellular processes is one of the most intriguing challenges in cell biology and medicine. Forefront approaches based on bioengineered nanoparticles might have the potential to target specific cell pathways, thus controlling downstream cell activities in a space and time selective fashion. The present project aims to develop and to validate a smart nanovectorable to activate a specific cell signalling and, on demand, to induce heat mediated cell death of nanovector targeted cells. As proof of concept, CONFINES is conceived to target the Wnt canonical pathway, one of the most studied and fascinating cell signalling, which orchestrates central mechanisms that govern cell proliferation, polarity and stem cell fate. To achieve the proposed objectives, a controlled synthetic approach will tailor Wnt ligands on magnetic nanoparticles, combining targeting and magnetic properties in a uniquenanovector. Owing to its chemico-physical features, NanoWnt will enable complete control of the cell signalling, and it will operate in vitro (human cell cultures) and in vivo (the aquatic invertebrateHydra vulgaris), in a dual mode: i) as an activator of the canonical Wnt pathway in those contexts where it is inactive ii) or upon exposure to a magnetic field, as a nanoheater, enabling specific cell ablation by hyperthermia. From a technological point of view, the project will advance basic knowledge on thermal ablation (via magnetic hyperthermia) and holds promises for translational medicine, providing a breakthrough tool to shape cell fate of nanovector receiving cells. Furthermore, combining diverse expertise, CONFINES will offer the applicant advanced and multidisciplinarytraining in the field of nanomaterial synthesis, characterization and functionalisation as well as in hyperthermia technology, which will complement his current skills based on nanobiotechnology and cellular/molecular biology.

Original text from CORDIS.

Participants

  • UNIVERSIDAD DE ZARAGOZA · ZaragozaCoordinatorSpain

Links

Data: CORDIS, © European Union