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

Abstract

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 β-galactosidase (β-Gal)-loaded ternary complex comprising tannic acid (TA) and phenylboronic acidconjugated polymers through sequential self-assembly in aqueous solution. At physiological conditions, the ternary complex exhibited a hydrodynamic diameter of ∼40 nm and protected the loaded β-Gal from unfavorable degradation by proteinase. Upon cellular internalization, the ternary complex recovered β-Gal activity by releasing the loaded β-Gal. The intravenously injected ternary complex thereby delivered β-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.

Lignocellulosic–biomolecules conjugated systems: green-engineered complexes modified by covalent linkers

“…5 Bioconjugated systems of (a) lignin, 117,118 (b) xylan, 121 and (c) tannic acid. 122 linker has cyclical ether functional groups that form ether bonds between xylan and gelatin. 41 Conversely, a singular linker is a tannic acid -a natural polyphenol studied in brush and nanoparticle structures.…”

“…121,123,124 In cancer treatment, for example, the tannic acid bioconjugated system showed less hepatoxicity than pure tannin acid. 122 Therefore, it is recommended that the risk assessment of lignocellulosic complexes be conducted in the early stages of developing so that their potential impacts on human health and the environment can be better evaluated.…”

Nanostructured particles assembled from natural building blocks for advanced therapies

“…353 Recently, a self-assembled ternary complex constructed from TA, enzyme (β-galactosidase), and phenylboronic acid-conjugated polymers were reported. 354 The obtained ternary complex could deliver β-galactosidase to the target tumor in a mouse model, protect the enzyme from degradation by proteinase, and release them upon cellular internalization.…”

Recent Progress in Protein-Polyphenol Assemblies for Biomedical Applications

“…The core−shell-type ternary complex GFP-TA@PEG with a hydrodynamic diameter of about 10− 20 nm had a less unfavorable interaction with serum; therefore, it had prolonged blood circulation and enhanced accumulation in tumors in a subcutaneous tumor model. Later, Honda et al 32 replaced GFP with β-galactosidase (β-Gal) to construct a pH-responsive enzyme delivery system for cancer treatment. The β-Gal-TA@PEG ternary complex had a hydrodynamic diameter of about ∼40 nm and protected β-Gal from decomposition by proteinase under physiological conditions, while upon cellular internalization, due to the decrease in pH, the β-Gal was released from the complex and recovered the enzymatic activity.…”