Post-doctoral allowance, 18 months - AAP 2017-1
Project leader : Patrick Couvreur
The use of biocompatible NanoMOFs (nanoparticles made of metal organic-inorganic frameworks) has been recently considered for applications in the nanomedicine field. The active collaboration between the Institut Galien and the Institut des Matériaux Poreux Paris has led to the efficient encapsulation of anticancer and antiviral compounds into NanoMOFs. Toxicological investigations, both acute and sub-acute, have proven the safety profile of nanoMOFs and the biodegradation pathway has been identified. Further in vivo experiments have recently demonstrated that NanoMOFs were able to target lung tissues and to efficiently treat an experimental lung tumor in mice.
The aim of the current project is to better understand, at the cellular level, how the nanoMOFs can interact with lung cancer cells. In vitro studies are routinely performed on 2D monocultures of isolated cancer cells. However, they do not show any structural architecture and lack the complex
physiology and the microenvironment of the real tumor tissues.The research project addresses this specific issue and proposes to apply 3D culture methodologies to construct a multicellular lung tumor model capable to reproduce in vitro the complex cancer cells/stroma cross-talk, therefore allowing to better understand how nanoMOFs can interact with the lung tumor tissue. The construction of the 3D model will rely on the assembly of cells in the form of multicellular tumor spheroïds. To achieve these objectives, the project will be organized around 3 main tasks: (1) the construction of the 3D lung tumor model, (2) the design of pH-sensitive nanoMOFs with different physico-chemical properties and (3) the investigation of the NanoMOFs on the 3D tumor model in vitro and prediction of the in vivo behavior.
This project will have scientific, technological, societal and economic impacts. In case of success, it will result in a more accurate evaluation of nanoMOFs therapeutic strategies, identifying the more efficient ones and making easier the decision of abrogating or promoting different preclinical assays. To be noted that this project will also allow to reduce the need for animals during preclinical studies and thus to observe the 3Rs (reduction, refinement and replacement) guiding principles for the use of animals in research according to the European rules and the legislation in force in France. In the long-term perspective, the use of lung cancer cells derived from patients will open the frontiers toward a personalized medicine with nanoMOFs, thus allowing to better tailor the therapy to each specific patient.