Harnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer

Yunjiao Zhang, Rui Sha, Lan Zhang, Wenbin Zhang, Peipei Jin, Weiguo Xu, Jianxun Ding, Jun Lin, Jing Qian, Guangyu Yao, Rui Zhang, Fanchen Luo, Jie Zeng (), Jie Cao () and Long-ping Wen ()
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Yunjiao Zhang: South China University of Technology
Rui Sha: School of Life Sciences, University of Science and Technology of China
Lan Zhang: University of Science and Technology of China
Wenbin Zhang: South China University of Technology
Peipei Jin: South China University of Technology
Weiguo Xu: Chinese Academy of Sciences
Jianxun Ding: Chinese Academy of Sciences
Jun Lin: School of Life Sciences, University of Science and Technology of China
Jing Qian: South China University of Technology
Guangyu Yao: School of Life Sciences, University of Science and Technology of China
Rui Zhang: South China University of Technology
Fanchen Luo: School of Life Sciences, University of Science and Technology of China
Jie Zeng: University of Science and Technology of China
Jie Cao: South China University of Technology
Long-ping Wen: South China University of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.

Date: 2018
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DOI: 10.1038/s41467-018-06529-y

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