Journal
NANOTECHNOLOGY
Volume 25, Issue 36, Pages -Publisher
IOP PUBLISHING LTD
DOI: 10.1088/0957-4484/25/36/365101
Keywords
autophagy; hepatocellular carcinoma; PAMAM dendrimers; oxidative stress
Funding
- Shanghai Science and Technology Funds [14431900200, 11431920104]
- National Key Basic Research Program of China [2013CB932502]
- School of Pharmacy, Fudan University
- Open Project Program of Key Lab of Smart Drug Delivery (Fudan University)
- Ministry of Education, China [SDD2013-02]
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Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.
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