Sequential Self-Assembly Using Tannic Acid and Phenylboronic Acid-Modified Copolymers for Potential Protein Delivery
Yuto Honda, Takahiro Nomoto, Makoto Matsui, Hiroyasu Takemoto, Yuka Kaihara, Yutaka Miura, Nobuhiro Nishiyama
Abstract
Tannic acid (TA) can form stable complexes with proteins, attracting significant attention as protein delivery systems. However, its systemic application has been limited due to nonspecific interaction. Here, we report a simple technique to prepare systemically applicable protein delivery systems using sequential self-assembly of a protein, TA, and phenylboronic acid-conjugated PEG-poly(amino acid) block copolymers in aqueous solution. Mixing the protein and TA in aqueous solution led to covering of the protein with TA, and subsequent addition of the copolymer resulted in the formation of boronate esters between TA and copolymers, constructing the core-shell-type ternary complex. The ternary complex covered with PEG exhibited a small hydrodynamic diameter of ∼10-20 nm and prevented an unfavorable interaction with serum components, thereby accomplishing significantly prolonged blood circulation and enhanced tumor accumulation in a subcutaneous tumor model. The technique utilizing supramolecular self-assembly may serve as a novel approach for designing protein delivery systems.