Note: Metastatic 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.
http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.pngJournal Article/Contribution to a conference proceedingsPallares, R. M. (Corresponding author)RWTH* ; Barmin, R. A.RWTH* ; Wang, A.RWTH* ; Kiessling, F.RWTH* ; Lammers, T. (Corresponding author)RWTH* Clinical cancer nanomedicines 2025CRSingapore 2025: Connecting Continents In Delivery Science, CRSingapore 2025, SingaporeSingapore, Singapore, 19 Feb 2025 - 21 Feb 20252025-02-192025-02-21Journal of controlled release385,113991(2025)[10.1016/j.jconrel.2025.113991]special issue: "Special Issue Celebrating The Success Of CRSingapore 2025 Conference / Guest Editors: Dr. Jiong-Wei Wang; Prof. Dr. Raymond Schiffelers; Professor Giorgia Pastorin; Prof. Dr. Gert Storm"2025 FilesBibTeX |
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