guest ::
000798313 001__ 798313 000798313 005__ 20230215042541.0 000798313 0247_ $$2CORDIS$$aG:(EU-Grant)864121$$d864121 000798313 0247_ $$2CORDIS$$aG:(EU-Call)ERC-2019-COG$$dERC-2019-COG 000798313 0247_ $$2originalID$$acorda__h2020::864121 000798313 035__ $$aG:(EU-Grant)864121 000798313 150__ $$aMacro-Nanomedicine to Treat Metastatic Cancer$$y2020-04-01 - 2025-03-31 000798313 371__ $$aUniversitätsklinikum Aachen$$bUKA$$dGermany$$ehttp://www.ukaachen.de/$$vCORDIS 000798313 372__ $$aERC-2019-COG$$s2020-04-01$$t2025-03-31 000798313 450__ $$aMeta-Targeting$$wd$$y2020-04-01 - 2025-03-31 000798313 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union 000798313 680__ $$aMetastatic cancer is a complex and highly heterogenous disease, which is very difficult to treat. The aim of the Meta-Targeting project is to establish a holistic, rational and realistic nanomedicine-based approach to improve the treatment of metastatic breast cancer. Concrete objectives are: (1) the development of polymeric micelles which can be efficiently and stably co-loaded with three different drugs and with an imaging agent; (2) the use of physical and pharmacological means to modulate the vasculature and microenvironment in tumors and metastases; (3) the identification of imaging- and biopsy-based biomarkers for patient selection; (4) the incorporation of drugs to overcome cellular and microenvironmental multidrug resistance; and (5) the implementation of multifunctional micelles to enhance the efficacy of immunotherapy. It is envisaged that micelles loaded with in-house developed doxorubicin prodrugs are able to induce immunogenic cell death in tumors and metastases without causing systemic immunodepression, that co-loading with the angiotensin receptor inhibitor losartan helps to prime tumors and metastases for improved delivery (of micelles, immunomodulatory antibodies and T cells), and that co-loading with the P-glycoprotein inhibitor tariquidar assists in inducing immunogenic cell death, while avoiding typical anti-Pgp side effects, such as neurotoxicity. Physical priming with ultrasound and microbubbles will promote the delivery of micelles, antibodies and T cells to and into primary tumors. Imaging- and biopsy-based biomarkers are needed to allow for patient stratification, which is critically important to improve the clinical translation of cancer nanomedicines. The outcomes of the different project lines in Meta-Targeting will - alone and especially together - be truly transformative: they will contribute to scientific and clinical progress in nanomedicine, in tumor-targeted drug delivery, in immunotherapy, and in the treatment of metastatic cancer. 000798313 909CO $$ooai:juser.fz-juelich.de:880760$$pauthority$$pauthority:GRANT 000798313 909CO $$ooai:juser.fz-juelich.de:880760 000798313 970__ $$aoai:dnet:corda__h2020::a893d0fb02a2e1e027f265e34e25d7b6 000798313 980__ $$aG 000798313 980__ $$aCORDIS 000798313 980__ $$aAUTHORITY