A new method was developed to fabricate nanospheres and vesicles as drug carriers. The drug-loaded nanospheres and vesicles were prepared by self-assembly of alginate in aqueous media containing Ca2+ and CO32− ions under very mild conditions. The preparation method did not involve any organic solvent and surfactant and could offer good control over the morphology and the size of self-assemblies. Through adjusting the preparation conditions, nanosized drug-delivery systems with different shapes, that is, nanospheres and vesicles, could be obtained. The morphologies of the drug-delivery systems were observed by transmission electron microscopy (TEM). 5-Fluorouracil (5-FU), an anticancer drug, was encapsulated in the nanospheres and vesicles, and in vitro drug release behavior was investigated. The effect of drug-loading content on the release was studied. The release of 5-FU could be effectively sustained from both drug-loaded nanospheres and vesicles because the presence of CaCO3 in the nanospheres/vesicles could reduce the permeability of the entrapped drug for the alginate-based self-assemblies.