Heat nano-sources for therapeutics – Nan'Onsen

This project is devoted to the elaboration of nano-objects associating gold nanoparticles (NPs) and thermosensitive polymers, then to the analysis of the conversion of light into heat in these nanohybrids and its application for biomedical purposes. Indeed, metal NPs under electromagnetic radiation are able to act as nanoscale heat sources due to a series of internal energy exchanges. This conversion process is very efficient when the light radiation frequency matches the NP surface plasmon resonance (SPR), which optimizes energy input. This can be employed in various fields, particularly for realizing optical, chemical or biological functions. Moreover, the optical properties of NPs can be used as probes of, either the local thermal energy variations in a medium, or the modifications of the medium morphology. One can then envisage materials or devices whose functionality is only activated and controlled by light.
Our nanohybrids consist of gold NPs on which chains of thermosensitive polymer are grafted. This kind of polymer exhibits in aqueous solution a hydrophilic-to-hydrophobic phase transition as the solvent temperature is raised above a certain value. In our nanohybrids, NPs overheat following light pulse absorption at the SPR; heat is then released through the interface toward the polymeric layer, the chains of which shrink around the NPs. The hydrophobic character acquired by the nanohybrids after this conformation change bestows them on efficient cell adhesion capacity and favors their dense self-assembling. This mechanism then enables us to attach a large number of NPs on the membrane of biological cells, rendering possible to subsequently destroy these cells by photo-induced local hyperthermia. The targeting of a tumor and its regression can thus be induced by light irradiation. We want to exploit these photothermal properties of our nanohybrids for biomedical purposes.
Our project objectives turn on four main points. (1) Elaboration of nanohybrids based on spherical and anisotropic gold NPs. (2) Validation of their biocompatibility. (3) Determination of the characteristics of the light-heat conversion and the nanoscale heat transfer, of their consequences on the hydrophobicity of the nano-objects and their self-assembly. (4) Photo-induced targeting of tumor cells in vitro and in vivo by nano-hybrids and optimization of a sequenced optical protocol for therapy by local hyperthermia.
To reach these objectives, we bring together the complementary skills of four partners:
• Partner 1: the Ecole Centrale Paris, with two teams specialized in nano-optics and nanoscale heat transfer,
• Partner 2: the Laboratoire de Chimie Physique (CNRS-Université Paris Sud) expert, for the project, in metal NP synthesis and in biophysics,
• Partner 3: the Ecole Supérieure de Physique et de Chimie Industrielles (UPMC, Ville de Paris, CNRS) for its expertise in the synthesis of metal NP-polymer nano-hybrids,
• Partner 4: the U728 (INSERM, Université Paris Diderot) having an expertise in animal models and analysis of heat-induced cell and tissue damages.