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Photothermal exposure of polydopamine-coated branched Au–Ag nanoparticles induces cell cycle arrest, apoptosis, and autophagy in human bladder cancer cells

Authors Zhao X, Qi T, Kong C, Hao M, Wang Y, Li J, Liu B, Gao Y, Jiang J

Received 16 May 2018

Accepted for publication 14 August 2018

Published 12 October 2018 Volume 2018:13 Pages 6413—6428

DOI https://doi.org/10.2147/IJN.S174349

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Linlin Sun


Xiaoming Zhao,1,* Tianyang Qi,1,* Chenfei Kong,1 Miao Hao,1 Yuqian Wang,1 Jing Li,1 Baocai Liu,2 Yiyao Gao,1 Jinlan Jiang1

1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China; 2Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun, China

*These authors contributed equally to this work

Purpose: Polydopamine-coated branched Au–Ag nanoparticles (Au–Ag@PDA NPs) exhibit good structural stability, biocompatibility, and photothermal performance, along with potential anticancer efficacy. Here, we investigated the cytotoxicity of Au–Ag@PDA NPs against human bladder cancer cells (T24 cells) in vitro and in vivo, as well as the underlying molecular mechanisms of photothermal therapy-induced T24 cell death.
Materials and methods: T24 cells were treated with different doses of Au–Ag@PDA NPs followed by 808 nm laser irradiation, and the effects on cell proliferation, cell cycle, apoptosis, and autophagy were analyzed. To confirm the mechanisms of inhibition, real-time PCR and Western blot analysis were used to evaluate markers of cell cycle, apoptosis, autophagy, and the AKT/ERK signaling pathway. Moreover, we evaluated the effects of the treatment on mitochondrial membrane potential and ROS generation to confirm the underlying mechanisms of inhibition. Finally, we tested the T24 tumor inhibitory effects of Au–Ag@PDA NPs plus laser irradiation in vivo using a xenograft mouse model.
Results: Au–Ag@PDA NPs, with appropriate laser irradiation, dramatically inhibited the proliferation of T24 cells, altered the cell cycle distribution by increasing the proportion of cells in the S phase, induced cell apoptosis by activating the mitochondria-mediated intrinsic pathway, and triggered a robust autophagy response in T24 cells. Moreover, Au–Ag@PDA NPs decreased the expression of phosphorylated AKT and ERK and promoted the production of ROS that function upstream of apoptosis and autophagy. In addition, Au–Ag@PDA NP-mediated photothermolysis also significantly suppressed tumor growth in vivo.
Conclusion: This preclinical study can provide a mechanistic basis for Au–Ag@PDA NP-mediated photothermal therapy toward promotion of this method in the clinical treatment of bladder cancer.

Keywords: nanoparticles, photothermal therapy, near-infrared laser, cell cycle, apoptosis, autophagy

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