The goal of the ERC Proof-of-Concept project "PIcelles" was to develop a micellar nanomedicine formulation that in addition to improving chemotherapeutic drug delivery to tumors also enables imaging for patient stratification and active enhancement of tumor penetration. To this end, the pi-pi stacking-stabilized polymeric micelle platform that is patent-protected by RWTH Aachen University was further functionalized in multiple different ways. To enable visualization and quantification of the target site accumulation of the micelles, a chelator has been incorporated in their hydrophobic core, and evidence for efficient and stable radiolabeling has been obtained. To achieve enhanced tumor penetration, (I) the micelles' hydrophilic shell has been modified with penetration-promoting peptides. In addition, (II) systematic studies were performed to reduce the diameter of the micelles and (III) to chemically engineer them in such a way that they are highly responsive to the slightly lower pH in the tumor microenvironment. We furthermore performed extensive market research, in order to identify the most optimal disease indications for clinical translation, the most appropriate developmental path, and the most suitable options for follow-up funding, out-licensing and partnering. Altogether, these efforts contribute to the development of next-generation nanomedicines that outperform current standard-of-care (nanomedicinal) anticancer drugs.
