Fabrication of injectable hydrogels from an anticancer peptide for local therapeutic delivery and synergistic photothermal–chemotherapy

Abstract

The susceptibility of anticancer peptides to proteolytic degradation is often considered as a major weakness that limits systemic therapeutic applications. However, localized delivery of anticancer peptides via injectable hydrogels is expected to improve drug efficacy and reduce systemic toxicity. Herein, an injectable hydrogel with drug releasing properties, NIR responsiveness and pH sensitivity was developed from an anticancer peptide (KL), Fe³⁺ ions and protocatechualdehyde via dynamic and reversible interactions. Benefiting from the formation of Fe(III)–catechol complexes between Fe³⁺ ions and protocatechualdehyde within gel networks, the obtained hydrogel exhibited intrinsic NIR absorption properties for photothermal ablation of tumor cells, and remote light control of drug release. Besides, the pH-labile imine bonds between KL and protocatechualdehyde endowed the injectable gel with pH sensitivity for sustained release of KL under a mildly acidic environment, inducing membrane destabilization and facilitating the cell uptake of DOX for combinational chemotherapy. Both in vitro and in vivo experiments revealed that the injectable hydrogel exhibited a synergistic therapeutic effect on inhibiting tumor growth via combinational photothermal–chemotherapy. Therefore, this work provides a promising attempt to develop a therapeutic hydrogel from an anticancer peptide, which could work as a localized drug delivery platform for synergistic photothermal–chemotherapy.