Acrylated Bioengineered Mussel Protein-Based Adhesive Nanoparticles for Locoregional and Sustained Drug Delivery

Nanoparticles have emerged as promising drug carriers owing to their ability to permeate cell membranes and enhance drug stability. However, their clinical application faces significant challenges, including rapid diffusion, inefficient retention at target sites, and burst drug release. This study proposes the use of adhesive nanoparticles derived from acrylated bioengineered mussel adhesive proteins (MAPs). Acrylic groups were conjugated to lysine residues in MAPs to form polyacrylate-MAPs by photo-cross-linking, retaining sufficient 3,4-dihydroxyphenylalanine residues for strong tissue adhesion in aqueous environments. These nanoparticles were designed to adhere effectively to the administration sites and facilitate continuous drug release. <i>In vitro</i> and <i>in vivo</i> evaluations demonstrated that the acrylated MAP-based nanoparticles exhibited superior wet adhesive properties, sustained drug release, and long-term retention at the administration site and effectively suppressed tumor growth, ensuring that a single dose maintained a therapeutic concentration at the target site over extended periods. Thus, this approach could address the challenges of drug localization and retention, significantly improving therapeutic efficacy. This study emphasizes the versatility of bioengineered MAP-based adhesive nanoparticles for locoregional and sustained drug delivery, with promising applications in cancer therapy, regenerative medicine, and other biomedical fields.