Switch of Surface Adhesion to Cohesion by Dopa-Fe³⁺ Complexation, in Response to Microenvironment at the Mussel Plaque/Substrate Interface

Although Dopa-Fe³⁺ complexation is known to play an important role in mussel adhesion for providing mechanical properties, its function at the plaque/substrate interface, where actual surface adhesion occurs, remains unknown, with regard to interfacial mussel adhesive proteins (MAPs) type 3 fast variant (fp-3F) and type 5 (fp-5). Here, we confirmed Dopa-Fe³⁺ complexation of interfacial MAPs and investigated the effects of Dopa-Fe³⁺ complexation regarding both surface adhesion and cohesion. The force measurements using surface forces apparatus (SFA) analysis showed that intrinsic strong surface adhesion at low pH, which is similar to the local acidified environment present during the secretion of adhesive proteins, vanishes by Dopa-Fe³⁺ complexation and alternatively, strong cohesion is generated in higher pH conditions similar to seawater. A high Dopa content increased the capacity for both surface adhesion and cohesion, but not at the same time. In contrast, a lack of Dopa resulted in both weak surface adhesion and cohesion without significant effects of Fe³⁺ complexation. Our findings shed light on how mussels regulate Dopa functionality at the plaque/substrate interface, in response to the microenvironment, and might provide new insight for the design of mussel-inspired biomaterials

Sprayable Adhesive Nanotherapeutics: Mussel-Protein-Based Nanoparticles for Highly Efficient Locoregional Cancer Therapy

Following surgical resection for primary treatment of solid tumors, systemic chemotherapy is commonly used to eliminate residual cancer cells to prevent tumor recurrence. However, its clinical outcome is often limited due to insufficient local accumulation and the systemic toxicity of anticancer drugs. Here, we propose a sprayable adhesive nanoparticle (NP)-based drug delivery system using a bioengineered mussel adhesive protein (MAP) for effective locoregional cancer therapy. The MAP NPs could be administered to target surfaces in a surface-independent manner through a simple and easy spray process by virtue of their unique adhesion ability and sufficient dispersion property. Doxorubicin (DOX)-loaded MAP NPs (MAP@DOX NPs) exhibited efficient cellular uptake, endolysosomal trafficking, and subsequent low pH microenvironment-induced DOX release in cancer cells. The locally sprayed MAP@DOX NPs showed a significant inhibition of tumor growth <i>in vivo</i>, resulting from the prolonged retention of the MAP@DOX NPs on the tumor surface. Thus, this adhesive MAP NP-based spray therapeutic system provides a promising approach for topical drug delivery in adjuvant cancer therapy