Magnetic nanoparticles (MNPs) are currently explored for use in biomedical applications, such as in MRI, hyperthermia and drug delivery. In this study, CoFe 2 O 4 and its calcium-substituted derivative viz. CS-Ca 0.5 Co 0.5 Fe 2 O 4 MNPs were synthesised via the glycol-thermal method. Furthermore, these MNPs were coated with chitosan (CS) to improve their biodegradability and biocompatibility. The anti-cancer drug, 5-fluorouracil (5-FU) was then loaded onto these MNPs to yield CS-Ca 0.5 Co 0.5 Fe 2 O 4 -5FU and CS-Ca 0.5 Co 0.5 Fe 2 O 4 -5FU. XRD results confirmed a single-phased cubic spinel structure for all MNPs. The naked MNPs displayed an average crystalline size of ~9.32 nm, which increased up to 18.20 nm upon coating. The VSM measurements recorded saturation magnetization values (Ms) of up to 73.951 emu/g. Upon polymer-coating, the shielding effect of chitosan resulted in reduced Ms of up to 17.220 emu/g in CS-Ca 0.5 Co 0.5 Fe 2 O 4 MNPs. Release profiles were determined at pH 4.5 and 7.4 over a period of 72 hours. A faster release of the drug was noted at the acidic pH with an accumulative release of 91.00% in CS-CoFe2O4-5FU. Coupled with a strong recommendation for in vitro studies, these MNPs present as attractive candidates to complement current anti-cancer treatments.