LAUSR

One key design feature in the development of any local drug delivery system is the controlled release of therapeutic agents over a certain period of time. In this context, we report the characteristic feature of a supramolecular filament hydrogel system that enables a linear and sustainable drug release over the period of several months. Through covalent linkage with a short peptide sequence, we are able to convert an anticancer drug, paclitaxel (PTX), to a class of prodrug hydrogelators with varying critical gelation concentrations. These self-assembling PTX prodrugs associate into filamentous nanostructures in aqueous conditions and consequently percolate into a supramolecular filament network in the presence of appropriate counterions. The intriguing linear drug release profile is rooted in the supramolecular nature of the self-assembling filaments which maintain a constant monomer concentration at the gelation conditions. We found that molecular engineering of the prodrug design, such as varying the number of oppositely charged amino acids or through the incorporation of hydrophobic segments, allows for the fine-tuning of the PTX linear release rate. In cell studies, these PTX prodrugs can exert effective cytotoxicity against glioblastoma cell lines and also primary brain cancer cells derived from patients and show enhanced tumor penetration in a cancer spheroid model. We believe this drug-bearing hydrogel platform offers an exciting opportunity for the local treatment of human diseases.