Supramolecular Hydrogel Based on Chlorambucil and Peptide Drug for Cancer Combination Therapy

Supramolecular hydrogels of self-assembling peptide–drug conjugates have been considered as effective self-delivery drug systems for cancer therapy in recent years. Here, a novel self-assembling peptide-based supramolecular hydrogel was developed by simultaneously conjugating small-molecule drug chlorambucil (CRB) and peptide drug tyroservatide (YSV) to the self-assembling peptide. The resulting hydrogel with a nanofiber structure showed enhanced stability against proteinase K degradation and an improved cellular uptake performance in comparison with the free molecules. As a consequence, it exhibited enhanced antitumor efficiency both in vitro and in vivo with favorable biocompatibility. This biocompatible self-delivery drug system could not only significantly improve the delivery efficiency of the small-molecule drugs but also adequately synergize the antitumor effect of CRB and YSV, inspiring the design of new strategies of cancer combination therapy.