Carrier-Free Supramolecular Hydrogel Composed of Dual Drugs for Conquering Drug Resistance

The resistance of tumor cells to anticancer drugs has become one of the principal causes of the failure in clinical chemotherapy. To overcome this issue, developing feasible drug delivery systems for effective cancer therapy is urgently needed. In this work, we construct an amphiphilic drug self-delivery system consisting of Taxol and tyroservatide (YSV) to overcome drug resistance. The carrier-free supramolecular hydrogel composed of nanofibers is formed by the involved ester bond self-hydrolysis process, which has high drug loading efficiency and facilitates the delivery of both the hydrophobic Taxol and hydrophilic YSV. Because of the dual inhibitory function of YSV on histone deacetylase and P-glycoprotein, an improved combinational anticancer effect of the molecule against drug-resistant tumor cells in vitro is achieved. Furthermore, the designed drug self-delivery system exhibited enhanced antitumor efficiency and favorable biocompatibility in vivo when administered by tail vein injection. Our study provides a new strategy for fabricating a carrier-free supramolecular hydrogel to overcome drug resistance, which might open up an alternative avenue for the tumor combinational therapy.