An inorganic-organic hybrid nanoparticle platform for tuneable, cell-type selective delivery of chemotherapy to pancreatic ductal adenocarcinoma (PDAC) tumors

• Applicants: Professorin Dr. Frauke Alves; Privatdozentin Dr. Lena-Christin Conradi; Professor Dr. Claus Feldmann
• Subject Area: Hematology, Oncology ; Solid State and Surface Chemistry, Material Synthesis ; Pharmacology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550628065

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year overall survival of 11%. It is expected to become the second cause of cancer deaths by 2040. Current PDAC therapy leans almost exclusively on surgery, radiotherapy and, very importantly, chemotherapy. Mainly gemcitabine, paclitaxel and combination regimens like FOLFIRINOX are being used. All are characterized by severe toxicity to healthy tissue and the occurrence of resistance. A particularly appealing approach to address these limitations is the formulation of chemotherapeutics in nanoparticles (NPs). This application proposes an innovative, inorganic-organic hybrid nanoparticle (IOH-NP)-based chemotherapy delivery system, that can be tuned to kill specific tumor-cell types or combinations of specific cell types. IOH-NPs have the advantage of combining unprecedented drug loading with low uptake in liver, kidneys and the reticuloendothelial system. We will rely on gemcitabine phosphate-based IOH-NPs and introduce cell selectivity by labeling the IOH-NPs with specific combinations of small molecules and peptides. The latter target membrane markers of 3 different tumor cell types: EGFR (cancer cells), FAP (cancer-associated fibroblasts) and PDGFR-beta (neovascular endothelium). The tuneability and efficacy of the delivery system will be evaluated in syngeneic and patient-derived PDAC models (tumoroids and murine models), but has very broad applicability in cancer therapy.

• DFG Programme: Research Grants
• International Connection: Belgium
• Cooperation Partner: Professor Dr. Pieter van der Veken