Supramolecular chemotherapy is a
strategy that is currently used
to improve the therapeutic efficacy of traditional chemotherapy while
mitigating side effects. Heptaplatin, a platinum chemotherapeutic
antitumor drug in colorectal tumors, is traditionally used in the
clinic. However, its side effects and low efficiency in killing tumors
remain unresolved. Herein, a facile supramolecular chemotherapy platform
on account of the host–guest chemistry between cucurbit[7]uril
and the commercially available heptaplatin was studied. At pH 7.4,
heptaplatin showed a strong binding to the cucurbit[7]uril nanocarrier
by 1H NMR, whose K
a was (1.38
± 0.06) × 106 M–1 by isothermal
titration calorimetry (ITC). At pH 6.0 in a tumor microenvironment,
overexpressed spermine can exchange competitively heptaplatin from
heptaplatin-CB[7]. This supramolecular complex achieved higher antitumor
activity on colorectal tumor cells and lower cytotoxicity than the
drug alone on colorectal normal cells. Furthermore, the antitumor
mechanisms of supramolecular complex were investigated by apoptosis,
cell cycle, and spermine synthase. It was found that heptaplatin-CB[7]
consumed more colorectal tumorous intracellular spermine by the spermine
synthase assay (413.85 ± 0.004 pg/mL); hepataplatin-CB[7] caused
early apoptosis (87.73%) of colorectal tumor cells; heptaplatin-CB[7]
induced an inhibitory response in the G1 phase of the tumor
cell cycle. These findings demonstrated that heptaplatin-CB[7] had
higher antitumor activity toward human colorectal tumor cells but
lower cytotoxicity toward human colorectal normal cells. It is expected
to promote the supramolecular chemotherapy and translational development
of the nanocomplex into the clinical field.
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