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.

With the increasing application of nanomaterials in aerospace technology, the long-term space exposure to nanomaterials especially in the space full of radiation coupled with microgravity condition has aroused great health concerns of the astronauts. However, few studies have been conducted to assess these effects, which are crucial for seeking the possible intervention strategy. Herein, using a random positioning machine (RPM) to simulate microgravity, we investigated the behaviors of cells under simulated microgravity and also evaluated the possible toxicity of titanium dioxide nanoparticles (TiO₂ NPs), a multifunctional nanomaterial with potential application in aerospace. Pulmonary epithelial cells A549 were exposed to normal gravity (1 g) and simulated gravity (~10⁻³ g), respectively. The results showed that simulated microgravity had no significant effect on the viability of A549 cells as compared with normal gravity within 48 h. The effects of TiO₂ NPs exposure on cell viability and apoptosis were marginal with only a slightly decrease in cell viability and a subtle increase in apoptosis rate observed at a high concentration of TiO₂ NPs (100 μg/mL). However, it was observed that the exposure to simulated microgravity could obviously reduce A549 cell migration compared with normal gravity. The disruption of F-actin network and the deactivation of FAK (Tyr397) might be responsible for the impaired mobility of simulated microgravity-exposed A549 cells. TiO₂ NPs exposure inhibited cell migration under two different gravity conditions, but to different degrees, with a milder inhibition under simulated microgravity. Meanwhile, it was found that A549 cells internalized more TiO₂ NPs under normal gravity than simulated microgravity, which may account for the lower cytotoxicity and the lighter inhibition of cell migration induced by the same exposure concentration of TiO₂ NPs under simulated microgravity at least partially. Our study has provided some tentative information on the effects of TiO₂ NPs exposure on cell behaviors under simulated microgravity.