An injectable PC₁₀ARGD/Cu²⁺/DOX hydrogel for combined chemodynamic and chemotherapy of tumors

Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC₁₀ARGD/Cu²⁺/DOX based on Cu²⁺, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC₁₀ARGD was prepared. First, Cu²⁺ was attached to the histidines in the PC₁₀ARGD polypeptide by the coordination reaction to form PC₁₀ARGD/Cu²⁺ hydrogel, then the PC₁₀ARGD/Cu²⁺/DOX hydrogel was prepared by encapsulating the DOX into the PC₁₀ARGD/Cu²⁺ hydrogel. The results of scanning electron microscopy showed that the PC₁₀ARGD/Cu²⁺/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC₁₀ARGD/Cu²⁺/DOX hydrogel could continuously produce ·OH in the presence of H₂O₂. In vitro MTT results showed that the PC₁₀ARGD/Cu²⁺/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC₁₀ARGD/Cu²⁺/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC₁₀ARGD/Cu²⁺/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC₁₀ARGD/Cu²⁺/DOX hydrogel possessed good biocompatibility.