부산대학교 도서관

Glioma stem cells (GSCs) are major contributors to the recurrence and drug resistance of glioblastoma (GBM) and are therefore a key target for GBM treatment. However, due to the therapeutic resistance of GSCs, innovative and efficient clinical treatment tools to eliminate GSCs are urgently needed. Photodynamic therapy (PDT) is a new strategy for killing GSCs because of its high safety and sensitive targeting ability. However, the existing photosensitizers applied to kill GSCs generally lack long-wavelength excitation light with effective tissue penetration, which prevents their effective application in vivo. Hence, a novel near-infrared light (NIR)-activated photosensitive drug was developed from upconversion nanoparticles (UCNPs), Pluronic F127 (F127) and curcumin (Cur) to form UCNPs-F127@Cur. This hybrid nanodrug significantly promoted the apoptosis of GSCs, increased the production of intracellular reactive oxygen species, inhibited the expression of pluripotency-related genes in GSCs, and inhibited the growth of transplanted GSCs into tumors in vivo under 980 nm excitation light. However, UCNPs-F127@Cur did not exert the above anti-GSC effects without excitation by 980 nm light. Transcriptome sequencing analysis revealed that PDT with UCNPs-F127@Cur could cause cell cycle arrest and induce the differentiation of GSCs by suppressing the Wnt-β-catenin and Jak-Stat signaling pathways. In conclusion, we constructed a novel NIR-activated, targeted GSC-killing hybrid nanodrug and elucidated its molecular mechanism, thereby providing a new strategy for the treatment of GBM.Graphical abstract: UCNPs-F127@Cur activated by NIR light with good tissue penetration were constructed and shown to effectively eliminate GSCs by inducing cell apoptosis, arresting cell cycle progression and the self-renewal of GSCs both in vivo and in vitro.