Breast cancer is a heterogeneous disease that accounts for 30% of all cancers diagnosed in women and over half a million deaths per year. Breast cancer stem cells (BCSCs) make up a small subpopulation of cells within a tumor are responsible for tumor initiation, formation, and recurrence. BCSCs have been the subject of concentrated research as potential targets for breast cancer therapies.
Precision targeting allows delivering smaller total doses to precise locations in the body. Hence, an intense prominence needs to be placed on the development of strategies that selectively and preferentially deliver the therapeutic agents to the target site simultaneously reducing the access to non-target sites.
The use of Molecularly Imprinted Polymer (MIP) in cancer treatment is a new line of research. The imprinting process consists in the polymerization of a functional monomer in the presence of the desired molecule with a cross-linking agent. After the extraction of the molecule, the polymer matrix contains tailor-made binding sites, complementary to the molecule.
The goal of the MAGnetic Molecularly Imprinted Polymer (MAGMIP) project is to propose a new concept for PROTEIN TARGETING and DRUG DELIVERY by taking advantages of the exceptional RECOGNITION PROPERTY of pMIP and of the LOCAL HEATING PROPERTY of magnetic nanoparticles under AMF for DRUG RELEASE sequestered in the MIP. In this project, we plan to combine in one magnetic nanomaterial: i) Recognition of metastatic tumor cells through a membrane receptor expressed on these cells by means of molecularly imprinted polymers covering the surface of magnetic nanoparticles; ii) monitoring the nanoparticle by its intrinsic fluorescence; iii) on-demand delivery in a controlled time manner of the encapsulated therapeutics upon alternative magnetic field stimulation. Our approach potentially transforms unspecific therapeutic agents with pronounced side effects into targeted therapeutic system useful for precision medicine. The combination of MIP with magnetic nanoparticles will then trigger a spatio-temporal release of drugs by taking advantage of the local heating properties of the magnetic nanoparticles.
To target BCSCs, we will imprint the cell surface protein CD44, a major marker of BCSCs and use drugs already tested in clinical trials to target BCSCs such as dasatinib, etomoxir or metformin. The ultimate goal of the proposal will be to develop innovative nanomaterials to reduce metastasis and treatment resistance in breast cancer.
The innovative aspect of the material relies in:
- imprint targeting which is conceptually radically different from recognition targeting between a ligand and a substrate
- release the drug based on a physical principle: breaking of weak bonds by local temperature rise.
Madame Nebewia GRIFFETE (PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
PHENIX PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX
Help of the ANR 216,188 euros
Beginning and duration of the scientific project: September 2021 - 42 Months