Fabrication of a multifunctional nanomaterial from a mussel-derived peptide for multimodal synergistic cancer therapy

• A mussel-derived peptide with good physical properties was synthesized. • The self-assembled peptide exhibited photothermal and chemodynamic activities. • Synergistic therapies on tumor cells were performed by the self-assembled peptide. Development of biocompatible and cell-targeting nanomaterials with multimodal therapeutic approach is important to cancer treatment by overcoming its multidrug resistance. Herein, we designed and synthesized a novel multimodal therapeutic nanomaterial from a mussel-derived peptide with good biocompatibility, cell-targeting ability, and self-assembling property. Relying on Fe(III)-catechol coordination and other noncovalent interactions, the mussel-derived peptide can self-assemble to form Fe(III)-DA complexes with intrinsic photothermal and chemodynamic activities in its nanoparticle. Because of the pH-responsive property, the nanoparticle disassembled to release doxorubicin (DOX) and ferric ions under acidic intracellular environment, inducing cellular apoptosis and elevating the cellular oxidative level (ROS) via iron-mediated Fenton reactions. Besides photothermal ablation, the heat generated by Fe(III)-DA complexes from NIR irradiation could increase the DOX-induced antitumor activity, and enhance the efficiency of the Fenton reaction for chemodynamic therapy, realizing synergistic treatment of cancer cells with minimal side effects.