A Modular Polysaccharide Platform With Tannic Acid‐Driven van der Waals Lock‐In for Programmable Protein Delivery

ABSTRACT

Protein delivery systems face persistent challenges, including low encapsulation efficiency, limited targeting ability, and lack of generalizability. Here, we propose a modular and programmable polysaccharide‐based platform, enabling efficient encapsulation of a wide range of proteins, and tunable targeting across different cell types. The stepwise assembly applies tannic acid (TA) for protein surface stabilization. This rewires the encapsulation mechanism from unstable electrostatic binding to robust van der Waals‐driven protein lock‐in. The TA‐protein complex can be encapsulated in an interchangeable polysaccharide nano‐framework, exploiting the lectin‐glycan recognition pattern to direct cell‐ and disease‐specific targeting. The TA‐Polysaccharide Encapsulation (TAPE) system robustly achieves > 85% encapsulation efficiency (EE) across a range of proteins, and tailoring the polysaccharide choice enables programmable targeting to distinct cell types. As a proof of concept, hirudin‐loaded TAPE achieved targeted anticoagulant treatment in vivo. Overall, our work positions TAPE as a simple and generalizable platform that overcomes fundamental barriers in protein delivery, offering wide translational potential for protein‐based therapies.