Matrix metallopeptidase 2-responsive curcumin-loaded nanoparticles-induced signal transducer and activator of transcription 3 inhibition suppresses glioblastoma multiforme growth via enhancing nuclear factor erythroid 2-related factor 2 activity

作者：Fujie Jia, Yingpeng Peng, Xiaobing Li, Shuai Yang, Yuping Xie, Yuanyuan Han, Mingsheng Huang, Tingyao Liu, Wei Zou, Lei Chen, Zibin Liang · 发表于：International Journal of Biological Macromolecules · 年份：2025 · DOI：10.1016/j.ijbiomac.2025.141998 · 被引用次数：7 · 研究领域：Curcumin's Biomedical Applications、RNA Interference and Gene Delivery、Signaling Pathways in Disease

This study investigated the inhibitory effects of matrix metallopeptidase 2 (MMP2)-responsive curcumin-loaded nanoparticles on glioblastoma multiforme (GBM), and elucidated their underlying mechanisms. The methods employed included the Cell Counting Kit-8 viability assay, colony formation assay, flow cytometry for apoptosis analysis, wound healing migration assay, quantitative real-time polymerase chain reaction, western blotting for gene expression profiling, mitochondrial function assessment, and in vivo antitumor efficacy evaluation. Curcumin significantly reduced the viability, proliferation, and migratory capacity of murine glioma cells (GL261). It also induced apoptosis, disrupted mitochondrial function, and increased reactive oxygen species levels. Notably, curcumin upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression while inhibiting signal transducer and activator of transcription 3 (STAT3) activation. The synthesized MMP2-responsive curcumin nanoparticles (Cur-NPs) effectively suppressed tumor growth and prolonged survival in a GBM mouse model. These data suggest that curcumin inhibits STAT3 activity via an Nrf2-dependent mechanism. This study advances our understanding of the mechanism of action of curcumin and suggests potential avenues for the development of targeted therapies for GBM.