Injectable pH-responsive polypeptide hydrogels for local delivery of doxorubicin

Abstract

Cancer, as a global health threat, is often treated with chemotherapy, but its effect is limited, especially the drugs such as doxorubicin (DOX) are limited by their non-specificity and side effects. This study focuses on developing a new drug delivery system to overcome these challenges. Based on the self-assembling peptide hemopressin (HP), we designed and screened FOK peptide, which serves as a pH-responsive carrier with excellent pH sensitivity and mechanical stability. At a concentration of 20 mg mL⁻¹, FOK can spontaneously form a stable hydrogel, efficiently encapsulating DOX with an encapsulation rate exceeding 95%. This system can gradually release the drug in the tumor-specific mildly acidic environment, achieving precise delivery and sustained release of the drug. Rheological analysis revealed the superior mechanical and self-healing properties of FOK hydrogel, suitable for injection delivery with long-lasting stability. Mouse experiments showed that DOX/FOK hydrogel significantly inhibited tumor growth while greatly reducing toxicity. In conclusion, FOK hydrogel, as a delivery vehicle for DOX, not only optimizes the precise delivery and sustained release mechanism of DOX, but also reduces treatment side effects, opening up new avenues for the application of peptide hydrogels in cancer therapy and providing a scientific basis for designing efficient drug delivery systems.