Figure 7 In vitro biocompatibility of beta-CD nanocage (a).
Schematic illustration of drug release of beta-CD nanocage in the acidic
and reductive microenvironment of tumor cell (b). In vitro antitumor
effect of DOX-loaded beta-CD nanocage in acidic environment (c),
reduction environment (d) and normal physiological environment (e) as
well as the in vitro antitumor effect of free DOX (f).
3.4 Intracellular fluorescence imaging analysis of coumarin 6-loaded
beta-CD nanocage
To determine whether the beta-CD nanocage could enhance DOX release in
acidic or GSH-specific cellular microenvironments, intracellular
fluorescence imaging was conducted to evaluate the two distinct
responsive properties of the beta-CD nanocage. Tumor cell environments
were induced to intensify acid and GSH expression. Specifically, in
acid-treated tumor cells, green fluorescence was evident at 3 h and
continued to increase at 6 h, indicating that H+triggered the breakage of imine bonds, causing the nanocage to gradually
disintegrate and release coumarin 6. When tumor cells were treated with
GSH, the green fluorescence signal was also evident and increased over
time, indicating that disulfide bonds also underwent breakage in the
enhanced reducing environment, allowing coumarin 6 to escape from the
beta-CD nanocage. In untreated tumor cells, the fluorescence was lower
compared to acid- or GSH-treated tumor cells, and the contrast between
treated and untreated groups was noticeable. These results demonstrated
that beta-CD is highly sensitive to acidic and GSH environments.
Therefore, the enhanced intracellular drug release and uptake could be
improved using this proposed beta-CD nanocage.