Integrated Microsystems for In silico Modeling and in vitro assessment of nanoparticle TrAnsport & radioTherapy Efficacy – IMITATE

Despite an increasing number of innovative therapeutic strategies, the large majority of drug candidates fail in clinical trials. This is particularly important for nanotherapeutics that are used as drug carriers or therapeutic agents to selectively kill cancer cells. This failure is largely due to difficulties to accurately model and predict the distribution of nanoparticles in vivo and their therapeutic efficacy.
The IMITATE project will develop an integrated 3D in vitro platform enabling the prediction of patient-cell response to nanotherapeutics, by reproducing the in vivo hypoxic, metabolic and mechanical environment. The platform will couple in silico and in vitro approaches to decipher nanoparticle transport and radiotherapy efficacy in situ, within a reproduced 3D physiological context, including a precise control not only in terms of chemistry and biology, but also in terms of mechanics (stiffness, stress) and transport of molecules (through a porous material away from the flow).
The transport of two types of nanoparticles will be studied: (1) AGuIX® nanoparticles, currently under clinical trials. (2) Fluorescent polymeric nanoprobes, with tunable physicochemical properties to unravel the influence of size, charges and functional group on nanoparticles transport and internalization within deep tissue layer.
IMITATE will guide future nanotherapeutic generation by deciphering nanoparticles transport within tissue, and how it is related to their effective radiosensitivity.
The ground of this project is a newly developed agarose-based microsystem that provides a user-friendly platform for optical imaging High Content Screening. It enables spatio-temporal analyzis of fluorescent nanoparticles transport within 3D model tumors, with relevant statistics. It now calls for new engineering development to mimick key physiological players: the presence of a porous matrix surrounding the tumor, a flow at distance, and a mechanically confined and rigid environment.