| 저자(한글) |
Zhang, Xudong,Zhang, Hongqiu,Liang, Xin,Zhang, Jinxie,Tao, Wei,Zhu, Xianbing,Chang, Danfeng,Zeng, Xiaowei,Liu, Gan,Mei, Lin |
| 초록 |
Magnetite (iron oxide, Fe 3 O 4 ) nanoparticles have been widely used for drug delivery and magnetic resonance imaging (MRI). Previous studies have shown that many metal-based nanoparticles including Fe 3 O 4 nanoparticles can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. To investigate the biosafety of Fe 3 O 4 and PLGA-coated Fe 3 O 4 nanoparticles, some experiments related to the mechanism of autophagy induction by these nanoparticles have been investigated. In this study, the results showed that Fe 3 O 4 , PLGA-coated Fe 3 O 4 , and PLGA nanoparticles could be taken up by the cells through cellular endocytosis. Fe 3 O 4 nanoparticles extensively impair lysosomes and lead to the accumulation of LC3-positive autophagosomes, while PLGA-coated Fe 3 O 4 nanoparticles reduce this destructive effect on lysosomes. Moreover, Fe 3 O 4 nanoparticles could also cause mitochondrial damage and ER and Golgi body stresses, which induce autophagy, while PLGA-coated Fe 3 O 4 nanoparticles reduce the destructive effect on these organelles. Thus, the Fe 3 O 4 nanoparticle-induced autophagosome accumulation may be caused by multiple mechanisms. The autophagosome accumulation induced by Fe 3 O 4 was also investigated. The Fe 3 O 4 , PLGA-coated Fe 3 O 4 , and PLGA nanoparticle-treated mice were sacrificed to evaluate the toxicity of these nanoparticles on the mice. The data showed that Fe 3 O 4 nanoparticle treated mice would lead to the extensive accumulation of autophagosomes in the kidney and spleen in comparison to the PLGA-coated Fe 3 O 4 and PLGA nanoparticles. Our data clarifies the mechanism by which Fe 3 O 4 induces autophagosome accumulation and the mechanism of its toxicity on cell organelles and mice organs. These findings may have an important impact on the clinical application of Fe 3 O 4 based nanoparticles. Graphic Abstract ACS Electronic Supporting Info |
