Development of a Green-synthesized GNP/CQD-reinforced TSP–GG Hydrogel Bead System for pH-sensitive and Sustained Doxorubicin Release in Colorectal Cancer Therapy

Colorectal cancer (CRC) therapy using doxorubicin (DOX) is often limited by systemic toxicity and non-specific drug release in the gastrointestinal tract. To address this challenge, a novel pH-responsive bio-nanocomposite hydrogel bead system was developed using tamarind seed polysaccharide (TSP) and gellan gum (GG) as the polymer matrix, reinforced with green-synthesized graphene nanoparticles (GNPs) reduced using cinnamon extract and coconut shell-derived carbon quantum dots (CQDs). The hydrogel beads were fabricated through ionic crosslinking with 4 wt.% CaCl₂ and characterized using FTIR, XRD, SEM–EDX, UV–Vis, and photoluminescence analyses. Swelling and in vitro drug release studies performed at pH 1.0, 6.6, and 7.2 demonstrated strong pH-responsive behavior, with a maximum swelling ratio of 1580% at pH 7.2. The nanocomposite exhibited 99% encapsulation efficiency and achieved 99% cumulative DOX release after 128 h under colonic conditions, while only 0.67% release occurred at pH 1.0, confirming effective protection in gastric environments. Additionally, the hydrogel showed notable antibacterial activity against E. coli and S. aureus, along with antioxidant activity (IC₅₀ = 5 mg/mL). Cytotoxicity studies on HT-29 colorectal cancer cells revealed controlled drug delivery, with IC₅₀ values of 48 µg/mL for free DOX and 96 µg/mL for DOX-loaded hydrogel, confirming sustained-release behavior. These results highlight the potential of the TSP–GG/GNP/CQD bio-nanocomposite hydrogel as a multifunctional and environmentally sustainable platform for colon-targeted drug delivery in colorectal cancer therapy.