Doxorubicin conjugated with nanodiamonds and in free form commit glioblastoma cells to heterodromous fates

作者：Chen, Zhuo; Wang, Chao; Li, Tong-Fei; Li, Ke; Yue, Yuan; Liu, Xin; Xu, Hua-Zhen; Wen, Yu; Zhang, Quan; Han, Min; Komatsus, Naoki; Xu, Yong-Hong; Zhao, Li^*; Chen, Xiao^*

来源：Nanomedicine, 2019, 14(3): 335-351.

DOI：10.2217/nnm-2018-0330

• apoptosis
• autophagy
• doxorubicin
• glioblastoma cells
• HMGB1
• nanodiamonds

Aim: To mechanistically compare the effects of doxorubicin (DOX) and DOX conjugated with nanodiamonds (Nano-DOX) on human glioblastoma cells (GC). Materials & methods: GC viablity,proliferation and activation of apoptosis and autophagy was assayed in response to DOX and Nano-DOX. Expression and release of HMGB1 were measured and its role in apoptosis and autophagy probed in response to DOX and Nano-DOX.Results: DOX induced apoptosis in GC while Nano-DOX induced autophagy. Inhibition of autophagy in Nano-DOX-treated GC promoted apoptosis. DOX suppressed the emission of HMGB1 while Nano-DOX stimulated HMGB1 emission which was attenuated when autophagy was repressed. Blocking of HMGB1 emission mitigated autophagy and enhanced apoptosis in Nano-DOX-treated GC. Exogenously administered HMGB1 promoted autophagy and protected against apoptosis in both Nano-DOX-treated GC and DOX-treated GC. Conclusions: Nano-DOX is a potent autophagy activator as opposed to DOX as an apoptosis inducer. Nano-DOX initiates a mutual reinforcement loop between autophagy and HMGB1 in GC and thereby protects GC against apoptosis.

• 出版日期2019-2
• 单位华中科技大学; 苏州大学; 武汉大学