Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu, China.
Department of Bioengineering and the California Nanosystems Institute, University of California, Los Angeles, CA, USA.
Nat Commun. 2019 Jul 11;10(1):3051. doi: 10.1038/s41467-019-11082-3.
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 WO 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.
由于严重的副作用，肝脏转移的治疗进展缓慢。在本研究中，我们展示了一种能够选择性消除转移性癌细胞的策略。通过组织蛋白酶 B 可切割肽将靶向细胞核的 WO 纳米颗粒（WONPs）与含有光敏剂（Ce6）的线粒体选择性介孔硅纳米颗粒（MSNs）连接起来。在肝细胞中，激光照射后，生成的单线态氧被 WONPs 消耗，进而导致其光热加热能力丧失，从而使肝细胞免受激光照射引起的热损伤。相比之下，在癌细胞中，被切割的肽接头允许 WONPs 和 MSNs 分别靶向细胞核和线粒体，从而可以发挥光动力和光热治疗的作用。这确保了癌细胞的能量产生可以被消除。我们还在基因和蛋白质水平上进一步评估了潜在的分子机制，以更好地理解治疗效果。
