FBR: Alexandre Detappe

Speaker: Alexandre Detappe
Gustave Roussy, Cancer campus, Paris, FR

Nanomedicine from Supramolecular Design to the Clinic

Talk abstract: Translating nanomedicine innovations into clinical reality requires bridging molecular-level design with therapeutic evaluation in patients. Our laboratory develops modular nanomedicine platforms rooted in supramolecular chemistry and advances them along the preclinical-to-clinical continuum.

Central to our work is a supramolecular peptide-based biofunctionalization strategy that allows the orientation-controlled display of targeting moieties, including single-domain antibodies directed against tumor-associated and immune cell antigens, on the surface of diverse nanoparticle scaffolds. This platform has been extended to engineer targeted high-Z radioenhancers for combined external-beam radiotherapy and MRI-guided radioligand therapy, revealing atomic-number-dependent mechanisms that govern radioenhancement at the nanoscale. In parallel, we study the intrinsic immunomodulatory properties of nanomaterials on primary human immune cells and show that drug-free nanoparticles can prime NK and T cell anti-tumoral responses, opening new directions for nanoimmunotherapy.

Our translational pipeline also includes combination bottlebrush prodrug nanomedicines for multiple myeloma, PROTAC-polymer conjugates for targeted protein degradation, and injectable polymer-nanoparticle hydrogels for subcutaneous antibody delivery. Several programs have reached clinical milestones: liposomal nanoformulations were tested in a phase I study in mechanically ventilated patients, ultrasmall gadolinium-based nanoparticles (AGuIX) are progressing through phase I/II radioenhancement trials across multiple indications, and polymer-nanoparticle hydrogel depots are being developed as subcutaneous delivery platforms for vesicant antibody-drug conjugates to enable at-home administration of hospital-restricted biologics.

These converging efforts show how supramolecular design, when embedded in a translational framework, can shorten the path from bench chemistry to patient benefit.