Drug-Bearing Supramolecular Filament Hydrogels for Local Treatment of Diseases

We report here the direct use of therapeutic agents to create self-assembling supramolecular filaments that can form hydrogels in physiologically relevant conditions. Our strategy is to chemically conjugate a short peptide onto a therapeutic agent to form a drug amphiphile for self-assembly into one-dimensional (1D) nanostructures. Through the choices of the peptide sequences and the manipulation of the assembly kinetics, we are able to tune the gelation conditions, the drug release rates, and other properties important for local delivery. In one specific example, we found that rationally designed camptothecin (CPT) amphiphiles could spontaneously form a viscous solution in water containing self-assembled CPT filaments. This solution gels immediately upon contact with body fluids or cell medium. We carefully studied their drug release kinetics and in vitro efficacy against brain primary cells, and evaluated its in vivo efficacy using a resection brain tumor mouse model. Our results suggest that these drug-bearing supramolecular hydrogels have enormous potential to improve the current standards for local treatment of many diseases including brain tumor.