Mussel-Inspired Protein Nanoparticles Containing Iron(III)-DOPA Complexes for pH-Responsive Drug Delivery

A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH‐responsive drug release exploits the pH‐dependent changes in the coordination stoichiometry of iron(III)–3,4‐dihydroxyphenylalanine (DOPA) complexes, which play a major cross‐linking role in mussel byssal threads. Doxorubicin‐loaded polymeric NPs that are based on FeIII–DOPA complexation were thus synthesized with a DOPA‐modified recombinant mussel adhesive protein through a co‐electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the FeIII–DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that FeIII–DOPA complexation can be successfully utilized as a new design principle for pH‐responsive NPs for diverse controlled drug‐delivery applications. Mussel‐inspired protein nanoparticles that are capable of pH‐responsive drug release were obtained by exploiting the pH‐dependent changes in the stoichiometry of iron(III)–DOPA complexes. Such doxorubicin‐loaded polymeric nanoparticles were synthesized through a co‐electrospraying process and shown to release doxorubicin at acidic pH values. DOPA=3,4‐dihydroxyphenylalanine.