Near-infrared light-activatable upconversion nanoparticle/curcumin hybrid nanodrug: a potent strategy to induce the differentiation and elimination of glioma stem cells

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.

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.