The Polymer Society of Korea

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Plant-derived phenolic agents, such as protocatechuic acid (PCA), show promise in HCC treatment but are limited clinically by poor targeting and rapid metabolism. To address these challenges, this study introduces a pH-responsive hydrogel (PA-CB-PCA) for PCA loading, enhanced bioavailability, and targeted tumor delivery.Boronobenzoic acid was conjugated to weight chitosan (CB), with PCA loaded via reversible boronate ester bonds, and crosslinked with protocatechualdehyde (PA) through boronate ester and Schiff-base linkages to improve stability and enable pH-triggered release. In vitro, the hydrogel exhibited shear-thinning injectability, 73% PCA release at pH 6.5,HCC cell targeting, and reduced viability, migration, and proliferation.In vivo, it reduced tumor burden, liver injury markers, inflammation, and fibrosis.This platform offers a promising strategy for phenolic drug delivery and HCC treatment.