[Mn(PaPy2Q)(NO)]ClO4, a Near-Infrared Light activated release of Nitric Oxide drug as a nitric oxide donor for therapy of human prostate cancer cells in vitro and in vivo

• Main Authors: Yuwan Zhao, Zhuo Li, Huancheng Tang, Shanhong Lin, Wenfeng Zeng, Dongcai Ye, Xin Zeng, Qiuming Luo, Jianwei Li, Zhixian Ao, Jierong Mo, Lixin Chen, Yiqiu Yang, Yunsheng Huang, Jianjun Liu
• Format: Article
• Language: English
• Published: Elsevier 2021-05-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Prostate cancer; NO prodrug; Near-infrared light sensitive; Nude mouse xenograft
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332221001736

This study was the first to investigate the synthesis of near-infrared light-sensitive NO prodrug [Mn(PaPy2Q)(NO)]ClO4, and detection the amount of NO released by the drug in different time and near infrared light (10 mW, 20 mW). It showed that with the increase of light power, the time required for the drug to release NO was shortened, and we selected 20 mW, 10 min as a follow-up study of light power and irradiation time while ensuring the near-infrared light did not affect tumor cells. The cells were irradiated with 20 mW of near-infrared light for 10 min at 6 h after treatment with the drug on PC-3, LNCaP and 22RV1 cells, and NO concentration and cell survival rate were tested at 12 h, 24 h and 48 h. Experiments showed that NO concentration remained stable within 48 h and [Mn(PaPy2Q)(NO)]ClO4 inhibited the proliferation of cells in a concentration and time-dependent manner. Then we also found that [Mn(PaPy2Q)(NO)]ClO4 increased the expression of apoptosis-related proteins (PARP, Bax, Caspase 3/9), inhibited the expression of BCl-2 and increased the activity level of Caspase 3/7, which showed [Mn(PaPy2Q)(NO)]ClO4 promoted prostate cancer cells apoptosis. Next, the results in xenograft mouse model showed that [Mn(PaPy2Q)(NO)]ClO4 also had anti-prostate cancer effects in vivo, and the NO concentration increased in the tumor after near-infrared light irradiation. After [Mn(PaPy2Q)(NO)]ClO4 treatment 6 weeks, tumor volume was significantly reduced, Ki67 and BrdU protein expression was significantly reduced. TUNEL assay results showed that [Mn(PaPy2Q)(NO)]ClO4 could promote the apoptosis of solid tumors in vivo and in a concentration-dependent manner.