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

• Published in: Nature communications Vol. 9; no. 1; pp. 4236 - 13
• Main Authors: Zhang, Yunjiao, Sha, Rui, Zhang, Lan, Zhang, Wenbin, Jin, Peipei, Xu, Weiguo, Ding, Jianxun, Lin, Jun, Qian, Jing, Yao, Guangyu, Zhang, Rui, Luo, Fanchen, Zeng, Jie, Cao, Jie, Wen, Long-ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 140/146; 147/143; 631/80/39; 639/301/357/354; 639/925/352/2733; 64/60; 96/1; 96/2; 96/31; Adenine; Alloys - chemistry; Alloys - pharmacology; Alloys - therapeutic use; Animals; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Blotting, Western; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cancer; Cell Survival - drug effects; Chemotherapy; Chloroquine; Copper; Copper - chemistry; Drug resistance; Drug Resistance, Neoplasm; Female; HeLa Cells; Humanities and Social Sciences; Humans; In Situ Nick-End Labeling; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, SCID; multidisciplinary; Nanoalloys; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Palladium; Palladium - chemistry; Palladium base alloys; Phagocytosis; Phototherapy - methods; Photothermal conversion; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Survival; Synergistic effect
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06529-y

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. “Conventional chemotherapy-photothermal therapy combination has limited efficacy in drug resistant cancers. Here they develop Copper-palladium tetrapod nanoparticles to overcome these challenges and show them to work in synergy with autophagy inhibitors to treat drug resistant cancers”