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, Long-ping Wen

Nature Communications  (2018) 9:4236 | DOI: 10.1038/s41467-018-06529-y
 

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.

全文链接：https://www.nature.com/articles/s41467-018-06529-y