Natural Biopolymer-Based Injectable, Self-Healing Hydrogel via Self-Assembly of Pectin and Quaternized Guar Gum for Targeted Treatment of Colon Cancer.

A biocompatible, injectable, and self-healing hydrogel was constructed via electrostatic self-assembly of anionic pectin (PEC) and cationic quaternized guar gum (QGG). The optimized PEC/QGG hydrogel (QPE5, 1:3.5 ratio) exhibited rapid gelation (1.5 min), high yield (95.7%), shear-thinning behavior (viscosity decrease from 430 to 1.7 Pa·s), and excellent self-healing with ∼90% recovery of compressive strength. Zeta potential analysis confirmed charge neutralization (+2.9 mV for QPE5), indicating strong electrostatic interactions. The hydrogel displayed pH- and enzyme-responsive degradation, with accelerated disintegration under acidic (pH 5.5) and pectinase-rich conditions. 5-Fluorouracil (5-FU) was loaded with encapsulation efficiency of ∼72% and loading efficiency of ∼15% for QPE3 formulation. Drug release was adequately described by kinetic models, with the best-fitting model depending on the release conditions. The hydrogel demonstrated excellent cytocompatibility (>80% cell viability) and hemocompatibility (<2% hemolysis), while enabling selective inhibition of CT-26 colon carcinoma cells (viability reduced to ∼40% with enzyme-triggered release). This PEC/QGG platform integrates injectability, self-healing, and colon-specific degradability, offering a promising approach for localized colorectal cancer therapy.