Selective growth inhibition of cancer cells with doxorubicin-loaded CB[7]-modified iron-oxide nanoparticles

Abstract

Cucurbit[7]uril-modified iron-oxide nanoparticles (CB[7]NPs) were loaded with doxorubicin hydrochloride (Dox) and tested as a drug delivery system. Dox was found to interact with the carbonyl-rich rims of the CB[7] macrocycles adsorbed on the surface of the nanoparticles. The Dox-loaded nanoparticles (Dox@CB[7]NPs) were stable at room temperature and physiological pH and released their Dox cargo under acidic conditions, in the presence of glutathione, or with heating. Dox@CB[7]NPs reduced the viability of HeLa and three other cancer-derived cell lines in vitro at lower IC₅₀ than free Dox. They were also nontoxic to C. elegans. The sensitivity of HeLa cells to Dox@CB[7]NPs was enhanced when the temperature was elevated by application of an alternating magnetic field. Thus, Dox@CB[7]NPs show promise as agents for the intracellular delivery of Dox to cancer cells, for the selective and controlled release of the drug, and, more generally, as a possible means of combining chemotherapeutic and hyperthermic treatment modalities.