Eradication of unresectable liver metastasis through induction of tumour specific energy depletion

Da Huo, Jianfeng Zhu, Guojun Chen, Qian Chen, Chao Zhang, Xingyu Luo, Wei Jiang, Xiqun Jiang (), Zhen Gu () and Yong Hu ()
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Da Huo: Nanjing University
Jianfeng Zhu: Nanjing University
Guojun Chen: University of California
Qian Chen: University of California
Chao Zhang: Nanjing University
Xingyu Luo: Nanjing University
Wei Jiang: Nanjing University
Xiqun Jiang: Nanjing University
Zhen Gu: University of California
Yong Hu: Nanjing University

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Treatment of liver metastasis experiences slow progress owing to the severe side effects. In this study, we demonstrate a strategy capable of eliminating metastatic cancer cells in a selective manner. Nucleus-targeting W18O49 nanoparticles (WONPs) are conjugated to mitochondria-selective mesoporous silica nanoparticles (MSNs) containing photosensitizer (Ce6) through a Cathepsin B-cleavable peptide. In hepatocytes, upon the laser irradiation, the generated singlet oxygen species are consumed by WONPs, in turn leading to the loss of their photothermally heating capacity, thereby sparing hepatocyte from thermal damage induced by the laser illumination. By contrast, in cancer cells, the cleaved peptide linker allows WONPs and MSNs to respectively target nucleus and mitochondria, where the therapeutic powers could be unleashed, both photodynamically and photothermally. This ensures the energy production of cancer cells can be abolished. We further assess the underlying molecular mechanism at both gene and protein levels to better understand the therapeutic outcome.

Date: 2019
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DOI: 10.1038/s41467-019-11082-3

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