Zhang Xiao, Guo Zhao, Liu Jing, Tian Gan, Chen Kui, Yu Shicang, Gu Zhanjun
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences, Beijing 100049, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences, Beijing 100049, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Bull (Beijing). 2017 Jul 30;62(14):985-996. doi: 10.1016/j.scib.2017.06.010. Epub 2017 Jun 23.
Near infrared (NIR) light-driven nitric oxide (NO) release nano-platform based on upconversion nanoparticles (UCNPs) and light sensitive NO precursor Roussin's black salt (RBS) was fabricated to generate NO upon 808nm irradiation. The application of 808nm laser as the excitation source could achieve better penetration depth and avoid overheating problem. The combination of UCNPs and RBS could realize the on-demand release of NO at desired time and location by simply controlling the output of NIR laser. Cellular uptake results showed that more nanoparticles were internalized in cancer stem-like cells (CSCs) rather than non-CSCs. Therefore, a synergistic cancer therapy strategy to eradicate both CSCs and non-CSCs simultaneously was developed. Traditional chemo-drug could inhibit non-CSCs but has low killing efficiency in CSCs. However, we found that the combination of NO and chemotherapy could efficiently inhibit CSCs in bulk cells, including inhibiting mammosphere formation ability, decreasing CD44/CD24 subpopulation and reducing tumorigenic ability. The mechanism studies confirmed that NO could not only induce apoptosis but also increase drug sensitivity by declining drug efflux in CSCs. This UCNPs-based platform may provide a new combinatorial strategy of NO and chemotherapy to improve cancer treatment.
基于上转换纳米颗粒（UCNPs）和光敏一氧化氮（NO）前体罗辛黑盐（RBS）构建了近红外（NIR）光驱动的NO释放纳米平台，在808nm激光照射下产生NO。应用808nm激光作为激发源可实现更好的穿透深度并避免过热问题。UCNPs与RBS的组合能够通过简单地控制近红外激光的输出，在所需的时间和位置实现NO的按需释放。细胞摄取结果表明，更多的纳米颗粒被癌症干细胞样细胞（CSCs）而非非癌症干细胞样细胞内化。因此，开发了一种同时根除CSCs和非CSCs的协同癌症治疗策略。传统化疗药物可抑制非CSCs，但对CSCs的杀伤效率较低。然而，我们发现NO与化疗的联合能够有效有效有效地细胞团中有效抑制CSCs，包括抑制乳腺球形成能力、减少CD44/CD24亚群以及降低致瘤能力。机制研究证实，NO不仅可诱导细胞凋亡，还可通过降低CSCs中的药物外排来提高药物敏感性。这种基于UCNPs的平台可能为改善癌症治疗提供一种新的NO与化疗联合策略。
