Non-Hemolytic Biomolecular Nanoarchitectures for Targeting Circulating Tumor Cells to Arrest Metastasis

"Metastasis is the leading cause of cancer-related deaths, primarily driven circulating tumor cells (CTCs) that migrate from the primary tumor site and colonize distant organs. Conventional therapies are often ineffective in efficiently targeting these CTCs, leading to cancer progression and recurrence. The TargetCTC proposes the development of anti-EpCAM nanobody-functionalized dendritic polyglycerol sulfate (dPGS)-based nanoarchitectures designed to specifically target CTCs using a novel ""hitchhiking"" strategy. These nanoarchitectures will attach to neutrophils - key players in the immune response that naturally interact with CTCs in the biological system. By hitchhiking on neutrophils, the designed advanced nanoarchitectures can circulate with immune cells in the bloodstream, enhancing their ability to detect and bind CTCs through the recognition of multiple sulfate groups and anti-EpCAM nanobodies. This approach not only improves targeting ability but also exploits the natural migration pattern of neutrophils, ensuring that nanoarchitectures are delivered directly to the target sites. To maximize therapeutic efficacy, nanoarchitectures will be made stimuli-responsive and loaded with doxorubicin. The dual functionality i.e., multiple sulfated groups and anti-EpCAM nanobodies, will allow nanoarchitectures to not only capture CTCs but also to deliver the drug to primary/metastatic tumors, leading to their targeted destruction. This innovative strategy to capture and neutralize CTCs while arresting primary/metastatic tumors could provide a groundbreaking approach in cancer treatment. This project aligns with the EU's endeavor in advancing cancer research and hold the potential of improving patient outcomes by inhibiting the spread of cancer at its earliest stages."