RESUMO
Twelve new hybrid compounds of Esculetin with nitric oxide (NO) donors and/or mitochondrial targeting groups were designed, synthesized, and evaluated for their anti-tumor activity and mechanism in vitro and in vivo. Notably, the most potent compound A11 exhibited nanomolar antiproliferative activity on triple-negative breast cancer (TNBC) MDA-MB-231 cells (IC50 = 8 nM) with a strikingly selective inhibitory effect. The mechanism of A11 involves targeting MDA-MB-231 cells' mitochondria, releasing a high NO concentration, and increasing the expression of cyclophilin D (CypD), leading to increased reactive oxygen species (ROS) and triggering cancer cell apoptosis. Additionally, A11 could arrest the cell cycle at the G2/M phase to achieve anti-tumor effects. Moreover, A11 demonstrated a superior TNBC inhibition rate and diminished toxicity relative to doxorubicin (DOX) in vivo. In summary, A11 serves as a noteworthy contender for TNBC treatment with high potency and minimal toxicity.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Apoptose , Ciclo Celular , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêuticoRESUMO
High-efficiency hybrid solar cells (HSCs) based on electrospun titanium dioxide (TiO2) nanofibers plus poly(3-hexylthiophene) (P3HT) are fabricated by means of both the pretreatment using tetrahydrofuran (THF) vapor and the surface modification using n-type antimony chalcogenide (Sb2S3) on the TiO2 nanofibrous networks. It is revealed that the THF pretreatment not only reinforces the interfacial physical contact but also suppresses the interfacial recombination. The Sb2S3 modification improves the light absorption and charge transfer. Given that the active layer of the HSCs is as thin as 300 nm, it is demonstrated that the power conversion efficiency (PCE) is enhanced over 175%, exhibiting a PCE of 2.32%.