Telomerase is constitutively overexpressed in the majority of human
cancers and
telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy.
BIBR 1532 is a well-known synthetic
telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of
telomerase. However, water insolubility of
BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-
tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive
drug delivery vehicle for improved transport, release and anti-
tumor effects of
BIBR 1532. Herein, ZIF-8 and
BIBR 1532@ZIF-8 were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of
BIBR 1532 in ZIF-8 coupled with an improved stability of
BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the
imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of
BIBR 1532 with more accumulation in the nucleus.
BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of
cancer cells as compared with free
BIBR 1532. A more potent inhibition on hTERT
mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in
BIBR 1532@ZIF-8-treated
cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.