Sequentially Self-Assembled Nanoreactor Comprising Tannic Acid and Phenylboronic Acid-Conjugated Polymers Inducing Tumor-Selective Enzymatic Activity

The construction of enzyme delivery systems, which can control enzymatic activity at a target site, is important for efficient enzyme-prodrug therapy/diagnosis. Herein we report a facile technique to construct a systemically applicable beta-galactosidase (beta-Gal)-loaded ternary complex comprising tannic acid (TA) and phenylboronic acid-conjugated polymers through sequential self-assembly in aqueous solution. At physiological conditions, the ternary complex exhibited a hydrodynamic diameter of similar to 40 nm and protected the loaded beta-Gal from unfavorable degradation by proteinase. Upon cellular internalization, the ternary complex recovered beta-Gal activity by releasing the loaded beta-Gal. The intravenously injected ternary complex thereby delivered beta-Gal to the target tumor in a subcutaneous tumor model and exerted enhanced and selective enzymatic activity at the tumor site. Sequential self-assembly with TA and phenylboronic acid-conjugated polymers may offer a novel approach for enzyme-prodrug theragnosis.