Beta-cyclodextrin-capped self-assembled zein nanoparticles for stable quercetin delivery

Quercetin (QR) holds a lot of promise for colorectal cancer therapy; however, its clinical efficacy is challenged by its limited solubility and chemical instability. To harness the anticancer potential of QR we have developed a macromolecular-based nanoparticle formulation, QRNP, encapsulating QR at high capacity. QRNP is composed of the natural plant-derived protein, zein, which self-assembles into a spherical structure via the nanoprecipitation technique. Beta-cyclodextrin (β-CD) was used as a capping agent to stabilize the nanoparticle surface and it served to enhance QR loading as well. Physicochemical characterization revealed QRNP's spherical morphology and confirmed its core-shell structure. QRNP exhibited a sustained biphasic release profile, enhanced colloidal stability, and enhanced metabolic stability. Encapsulation of QR in QRNP significantly reduced its IC₅₀ in HCT-116 and HT-29 colorectal carcinoma cells. QRNP triggered significant late-stage apoptosis as determined by flow cytometric analysis. These results support QRNP as an effective therapeutic against colorectal cancer.