Development and assessment of polyacrylamide-starch hydrogel nanocomposites with graphene quantum dots for targeted quercetin delivery to brain tumors

Brain carcinoma remains among the most challenging cancers to treat due to the restrictive blood-brain barrier (BBB), which limits drug bioavailability and durability. Quercetin (QC), a natural polyphenol with strong anticancer effects, suffers from poor BBB permeability. In this research, an innovative pH-sensitive hydrogel nanocomposite was engineered via physical cross-linking using a novel combination of polyacrylamide (PAM), starch (S), and graphene quantum dots (GQDs), serving as a promising nanocarrier for enhanced QC delivery. The uniqueness of this work lies in the synergistic integration of these specific materials through a newly implemented double emulsion method (W/O/W), enabling targeted, stable, and biocompatible drug transport across the BBB. The nanocomposite achieved exceptional encapsulation efficiency (EE) and loading efficiency (LE) of 89 % and 48 %, respectively—among the highest reported. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), and X-ray diffraction (XRD) analyses confirmed strong molecular interactions, favorable semi-globular nanoparticle morphology, and a mostly amorphous structure, respectively. The nanoparticles (NPs) exhibited an optimal size range of 42.68–58 nm with a low Polydispersity Index (PDI) of 0.28, indicating excellent dispersion. Dynamic light scattering (DLS) and zeta potential analysis (average: +53.3 mV) revealed high colloidal stability. Drug release was 46 % higher in tumor-simulated conditions after 96 h, reflecting targeted delivery potential. MTT assays on L929 (normal cells) and U-87 MG (cancerous cells) cell lines confirmed significant biocompatibility, with the QC-loaded nanocomposite showing 13 % reduced cytotoxicity compared to free QC on the L929 cell line. These findings support the potential of the developed nanocarrier as an efficient and targeted drug delivery platform for brain tumor therapy.