In this study, we report a new ultrashort
peptide (LOC), which forms a redox-sensitive
hydrogel after cross-linking with the mild
oxidant H₂ O₂ and used it for
tumor-targeted delivery of
doxorubicin hydrochloride (DOX). LOC gelled within a few minutes in low-concentration H₂ O₂
solution. The concentration of H₂ O₂ significantly altered the gelation time and mechanical properties of the
hydrogel. The in vitro micromorphology, secondary structure and rheology characterization of cross-linked
hydrogels confirmed the sensitivity and injectability to
reducing agent. The cross-linked
hydrogel had a strong drug loading capacity, and the drug was released in a GSH concentration-dependent manner, following the Fick diffusion model. In addition, the cross-linked
hydrogel showed no cytotoxicity to normal fibroblasts, and no damage to the subcutaneous tissue of mice was observed. In vitro cytotoxicity experiments showed that the DOX-
hydrogel system exhibited good anti-
cancer efficacy. In vivo studies using 4T1
tumor-bearing mice showed that the DOX-
hydrogel system had a significant inhibitory effect on
tumors. Therefore, the newly designed redox-sensitive
hydrogel can effectively enhance the therapeutic efficacy of DOX and reduce toxicity, making it an attractive biological material.