Performance of chelating agent modulated Β-cyclodextrin coated zinc ferrite nanocarriers for 5-FU delivery and cytotoxicity in glioblastoma

Glioblastoma multiforme (GBM) remains one of the most aggressive and therapeutically resistant primary brain malignancies, necessitating multifunctional nanoplatforms capable of controlled drug delivery and mechanistically validated cytotoxic action. In this study, we describe a chelating agent - driven synthesis of zinc ferrite (ZnFe 2 O 4 ; ZFO) nanoparticles coated with a bromocresol green functionalized β-cyclodextrin (BCG-β -CD) polymer, and we examine how chelating agent identity governs the thermal, structural, surface coating, and biological performance. Phase - pure cubic spinel ZnFe 2 O 4 was produced via sol-gel synthesis utilizing tartaric acid, citric acid, and glycine as chelating agents, confirmed by XRD and HRTEM, with the crystalline lattice fully preserved after polymer coating. Thermogravimetric measurements showed that the polymer fraction depended strongly on the chelating agent used during synthesis, with ~ 26% for BZTA and BZGLY, and ~ 45% for BZCA, while FTIR confirmed that surface attachment occurred through hydrogen-bond-mediated complexation without any distortion to the underlying ZFO lattice. All three nanocarrier systems achieved high 5-fluorouracil (5-FU) loading efficiencies (~ 80%), and in-vitro release experiments showed faster and more complete drug liberation under acidic, tumor - mimicking conditions at pH 6.2 than at physiological pH 7.4. Release rate correlated with coating thickness, as thinner-coated systems allowed quicker drug diffusion. Cytotoxicity evaluation in C6 glioblastoma cells confirmed that 5-FU loading substantially enhanced the anticancer effect of the carriers, with 5-FU@BZGLY recording the lowest IC 50 of 7.10 ± 0.40 µg mL − 1 .