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

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.

• Authors: Da Huo, Jianfeng Zhu, Guojun Chen, Qian Chen, Chao Zhang, Xingyu Luo, Wei Jiang, Xiqun Jiang, Zhen Gu, Yong Hu
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 3051 (07 11 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31296864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Oxides
• Photosensitizing Agents
• Reactive Oxygen Species
• Silicon Dioxide
• tungsten oxide
• CTSB protein, human
• Cathepsin B
• Tungsten

Topics

• Animals
• Cathepsin B (metabolism)
• Cell Nucleus (metabolism)
• Drug Carriers (chemistry, metabolism)
• Female
• HCT116 Cells
• Hepatocytes (cytology, metabolism)
• Humans
• Injections, Intravenous
• Lasers
• Liver (cytology, metabolism, pathology)
• Liver Neoplasms (pathology, secondary, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondria (metabolism)
• Nanoparticles (chemistry, metabolism)
• Oxidative Phosphorylation
• Oxides (chemistry)
• Photochemotherapy (instrumentation, methods)
• Photosensitizing Agents (administration & dosage)
• Reactive Oxygen Species
• Silicon Dioxide (chemistry)
• Treatment Outcome
• Tungsten (chemistry)
• Xenograft Model Antitumor Assays