Su Chen, Lin Jianhan, Li Cong, Wang Xinyu, Pan Donghui, Wang Lizhen, Xu Yuping, Chen Chongyang, Ji Kangfan, Wang Jinqiang, Chen Daozhen, Yang Min, Gu Zhen, Yan Junjie
Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi 214002, China.
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Asian J Pharm Sci. 2025 Apr;20(2):101018. doi: 10.1016/j.ajps.2025.101018. Epub 2025 Jan 10.
Nitric oxide (NO) modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies. Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules, such as short half-life, lipophilicity, non-selectivity, and poor stability, it remains challenging to prepare NO nanomedicines with simple composition, multiple functions and enhanced therapeutic efficacy. Herein, we build a liquid metal nanodroplet (LMND)-based NO nanogenerator (LMND@HSG) that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine) (HSG) ligand. Mechanically, the tumor microenvironment specifically triggers a cascade process of glutathione elimination, reactive oxygen species (ROS) generation, and NO release. According to actual demand, the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts. Along with the intrinsic anticancer property of LMND (ROS-mediated apoptosis and anti-angiogenesis), LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone. From this study, leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
一氧化氮（NO）调节多种与癌症相关的生理过程，并推动了癌症治疗绿色方法以及联合或协同治疗集成平台的发展。尽管已经提出了一种纳米工程策略来克服NO气体或小分子NO供体的缺陷，如半衰期短、亲脂性、非选择性和稳定性差等问题，但制备具有简单组成、多种功能和增强治疗效果的NO纳米药物仍然具有挑战性。在此，我们构建了一种基于液态金属纳米液滴（LMND）的NO纳米发生器（LMND@HSG），它由生物可还原的胍基化超支化聚（酰胺胺）（HSG）配体稳定。从机制上讲，肿瘤微环境特异性地触发了谷胱甘肽消除、活性氧（ROS）生成和NO释放的级联过程。根据实际需求，通过调整LMND和HSG的进料量可以很容易地控制ROS和NO的浓度。与单独的LMND和HSG相比，LMND@HSG给药除了具有LMND固有的抗癌特性（ROS介导的细胞凋亡和抗血管生成）外，还可以进一步增强对肿瘤生长的抑制作用。从这项研究来看，利用LMND进行NO气体治疗为基于LMND的抗癌纳米药物的前景提供了更多可能性。
