In vitro evaluation of bioinspired PEC/Zein/ZnO nanocarriers for pH-responsive curcumin delivery in colorectal cancer therapy

• A smart PEC/Z/ZnO nanocarrier was designed for pH-responsive curcumin delivery. • ZnO enhanced encapsulation efficiency and selective cancer cell cytotoxicity. • The system showed 97% drug release at pH 5.4, mimicking tumor microenvironments. • High biocompatibility was observed with over 85% L929 cell viability post-treatment. Colorectal cancer (CRC) remains a major global health challenge due to the limited efficacy and systemic toxicity associated with conventional therapies. In this study, a pH-responsive nanocarrier system was developed using pectin (PEC), zein (Z), and zinc oxide nanoparticles (ZnO) for the encapsulation and controlled release of curcumin (Cur), a hydrophobic compound with well-documented anticancer activity. The PEC/Z/ZnO@Cur nanocarriers were fabricated via a water-in-oil-in-water (W/O/W) double-emulsion technique and comprehensively characterized through physicochemical and morphological analyses. Fourier-transform infrared spectroscopy (FTIR) successful Cur encapsulation via hydrogen bonding and secondary non-covalent interactions, while X-ray diffraction (XRD) revealed suppressed Cur crystallinity and preserved ZnO crystal structure. Field-emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDX) verified the spherical morphology, surface roughness, and elemental distribution. Dynamic light scattering (DLS) indicated an average hydrodynamic diameter of approximately 270 nm, a polydispersity index (PDI) of 0.27, and a zeta potential of +47.1 mV, demonstrating strong colloidal stability and positive surface charge favorable for cellular interaction. Incorporation of ZnO significantly enhanced encapsulation efficiency (from 72.0% to 85.5%) and drug loading capacity (from 37.0% to 46.0%), confirming its structural and interactive contribution to Cur retention. In vitro release studies exhibited pH-dependent behavior, with accelerated drug release under acidic conditions (pH 5.4). The release kinetics followed the Korsmeyer–Peppas model at pH 7.4 and the Baker–Lonsdale model at pH 5.4, indicating diffusion- and swelling-controlled mechanisms, respectively. MTT assays confirmed high biocompatibility toward L929 fibroblast cells and selective cytotoxicity against HT-29 colorectal cancer cells. These in vitro results highlight the promise of PEC/Z/ZnO@Cur nanocarriers as pH-responsive systems for targeted curcumin delivery in colorectal cancer therapy, supporting their further investigation in 3D and in vivo preclinical models.