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

Abstract

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 Fe(III)-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 Fe(III)-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 Fe(III)-DOPA complexation can be successfully utilized as a new design principle for pH-responsive NPs for diverse controlled drug-delivery applications.

Mussel Byssus Structure‐Function and Fabrication as Inspiration for Biotechnological Production of Advanced Materials

“…A) PreCols purified from mussel foot tissue were drawn into anisotropic fibers with native‐like properties . B) Nanoparticles based on recombinant mfp‐1 were used for pH‐induced drug release, while rfp‐151, a recombinant fusion mfp‐1 and mfp‐5, was electrospun into nanofibers with polymer‐blending partners and can serve as a scaffold for bioactive molecules and cell growth . C) Peptides based on preCol His‐rich domains self‐assemble into free‐standing peptide‐films, the hierarchical architecture and mechanics of which can be tuned with metal ions .…”

“…A strategy to circumvent the inherent challenge of expressing very long and repetitive proteins is the biotechnological production of a shortened construct, in which tyrosine residues are modified to DOPA enzymatically in vitro following expression. For example, rfp‐1, a truncated variant of mfp‐1 comprising only 12 tandemly repeated decapeptides (AKPSYPPTYK) 12 was successfully produced and exploited in several studies . Following enzymatic modification of Tyr to DOPA, Fe 3+ could mediate strong bridging of rfp‐1 coated surfaces via DOPA‐iron complexation .…”

“…A potential medical adhesive and sealant based on rfp‐1 was developed in which gelation of concentrated rfp‐1 solution was mediated either by noncovalent Fe 3+ complexation or quinone‐mediated covalent cross‐linking, resulting in tunable viscoelastic and self‐healing behavior. The pH sensitivity of the DOPA‐Fe 3+ complex was exploited to develop an electrospraying process to synthesize polymeric nanoparticles based on rfp‐1 and doxorubicin, a commercial anti‐breast‐cancer drug, in which drug release was induced via pH‐dependent changes in DOPA‐metal coordination (Figure B) . The nanoparticles were efficiently taken up by cells and drug release resulted in a cytotoxic effect on the cancer cell line.…”

Smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release, photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma

“…Recently, stimuli-responsive drug delivery system (DDS) has captured extensive attentions due to their finely controllable response to external or tumor micro-environment stimulus, which could significantly reduce adverse effects and enhance their anti-cancer efficiency 12-17. To utilize the nature of tumor micro-environment, considerable efforts have been made to develop tumor micro-environment responsive strategies for cancer therapy, such as the redox-responsive DNA nano-hydrogels,18 the ATP-triggered Dox / Duplex nano-vehicles,19 the acid-degradable polymer nano-carriers,20,21 the enzymatic-mediated peptide / MSN nano-system22 and hypoxia-responsive nano-carrier system17, which were demonstrated the enhanced anticancer efficacy and reduced side effects to normal tissues. However, only few reported strategies have achieved for the programmable synergistic treatment of cancer to overcome the shortages of a single therapeutic modality.…”

Accelerated skin wound healing using electrospun nanofibrous mats blended with mussel adhesive protein and polycaprolactone

“…Additionally, MAPs have been considered as potential adhesive biomaterials due to their low immunogenicity in the human body, as well as their biocompatibility and biodegradability . Moreover, high production and versatile modification of the MAPs via recombinant DNA technology and bacterial expression systems have provided the opportunities to exploit MAPs as biomaterials for applications in diverse fields . Previously, mussel‐inspired, multi‐functional nanofibrous scaffolds based on recombinant MAPs have been reported, and their reinforced mechanical strength, biocompatibility, and sticky surface properties useful for the facile introduction of diverse biomolecules have gained much attention for potential applications in functional tissue engineering scaffolds .…”