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

• Published in: Advanced composites and hybrid materials Vol. 7; no. 3
• Main Authors: Jing, Guoxin, Li, Youyuan, Sun, Feiyue, Liu, Qiang, Du, Ai, Wang, Hong, Niu, Jintong, Lu, Jialu, Qian, Yechang, Wang, Shilong
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2024
• Subjects: Ceramics; Chemistry and Materials Science; Composites; Glass; Materials Engineering; Materials Science; Natural Materials; Polymer Sciences; Glioma stem cells; Curcumin; Photodynamic therapy; Photoswitch; Upconversion nanoparticles
• ISSN: 2522-0128; 2522-0136
• DOI: 10.1007/s42114-024-00886-7

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 .