The Uptake of Cucurbit[n]urils into Human Cells

Abstract

Cucurbit[n]urils (CB[n], where n = 5-8, 10, 13, 14, 15) are small, barrel shaped organic molecules that consist of two hydrophilic oxygen lined portals and a hydrophobic cavity. The many different applications of cucurbiturils include: the encapsulation of fluorescent dyes as biodiagnostics and molecular switches, as components in nanomachines, and as drug delivery vehicles. Proflavine (3,6-diaminoacridine) is a fluorescent DNA intercalator that can be encapsulated by CB[7]. In this study, CB[7]-encapsulated proflavine was used to elucidate the mechanisms by which cucurbiturils are taken into human embryonic kidney cells (HEK-293). When compared with free proflavine, CB[7]-encapsulated proflavine showed an increase in fluorescence intensity and a hypsochromic shift from 507 to 485 nm upon formation of the host-guest complex. The cellular uptake of the cucurbituril was monitored using fluorescence spectrophotometry using an optimised concentration of CB[7]-encapsulated proflavine (25 µM) and an incubation time of 25 min. Using HEK-293 cells that had been transfected with different solute carrier transporters, the organic anion transporter OATP2B1 statistically increases the uptake of CB[7]-encapsulated proflavine, while the OCT3 and OATP1A2 transporters resulted in a statistically reduced uptake of the macrocycle.