MicroNanoCell

One of the strengths of the field of nanomedicine is its promise to bring new therapies to a site, by remote activation of nanomaterials to produce for example heat or chemical reactions, while reducing side effects. The current challenge of these "physical nano-therapies" is to improve their therapeutic efficacy. To do this, a modern track is to produce nanohybrids with several therapeutic functions, ultimately amplifying their therapeutic potential. Gold nanoparticles (NPs) (plasmonics), iron oxide nanoparticles (magnetic) and copper sulphide (plasmonic semiconductors) are the most modern theranostic agents. Each of these individual nanoparticle provides a number of modalities and functions. Among others; magnetic manipulation, MRI imaging, magnetic heating for magnetic NPs, phototothermia and detection for gold NPs, and finally photothermia and photodynamic therapy for copper sulphide. Here, we propose a new generation of optimized magneto-plasmonic nanohybrids combining the three materials into a single plasmonic (metal and semiconductor) and magnetic ternary hierarchical nanostructure to enable both magnetic therapy (hyperthermia) and two laser-assisted therapies (photothermia and dynamic photothermia). This ternary association, which is unprecedented, should give rise to synergistic physical properties due to interactions between the individual components, transcending their individual assets. Nevertheless, for such multifunctional "lab-on-a-nanoparticle" to have a clinical use one day, two challenges must first be addressed for, which are often ignored because of their difficulty in putting into practice: First, the lack of reproducibility of syntheses of multifunctional nano-objects once transposed on a larger scale. Then, the potential biological instability of these nanohybrids when they come into contact with the bio-environment, leading to biotransformations and biodegradations that can strongly impact their therapeutic properties. In this context, MicroNanoCell aims to (i) propose a modular microfluidic platform combining high throughput chemical synthesis of tri-therapeutic nanohybrids and screening of their biotransformations under biomimetic conditions; (ii) to compare bio-microfluidic screening with intracellular fate by proposing observations and measures, in situ, at the heart of living cells, of nanobiotransformations of hybrids; and finally (iii) to explore completely new strategies taking advantage of the complexity of the cellular environment to (re) model nanohybrids into unique bio-validated structures, either by microfluidics or by using multicellular spheroids as bio tools.