Exploring pH‐Responsive Encapsulation and Release of 5‐Fluorouracil Molecules From Yoctowell Cavities

ABSTRACT 5‐Fluorouracil (5‐FU) is a chemotherapeutical agent that has been used to treat cancer for several decades, however, its therapeutic efficiency has been hampered by its short half‐life, limited bioavailability, rapid metabolism and the development of drug resistance. Yoctowells, which are surface engineered cavities with internal volumes in the yocto range (∼10 −24 L), are designed to release molecules within a controlled pH range. This manuscript demonstrates encapsulation of the anticancer drug 5‐FU within a yoctowell and its pH‐sensitive release from the yoctowell. UV–vis and fluorescence spectroscopic results using a porphyrin base molecule as a fluorescent sensor demonstrate that 5‐FU is contained within the yoctowell at physiological pH (pH = 7.2). At acidic pH (pH = 3.0), 5‐FU is released with 99.5% efficiency after 12 h. The sustained release profile indicates a pH‐dependent response change from 3.0 to 7.2, with an increase in release rate as the acidity increases, and an average release of ∼4 molecules from each yoctowell cavity. In contrast, no release was observed at neutral (pH = 7.2) and basic pH (9.0). These results indicate that yoctowells are potential carriers of 5‐FU for cancer treatment with a controlled pH, presenting the possibility of better control and targeting in chemotherapeutical procedures in the future.