Chen Ying, Jin Yanxia, Wang Weidong, Zhang Yueyang, Sun Hui, Wu Aobo, Zhu Haibo, Gong Yongsheng, Wang Xiaoyu, Tian Leyi, Pan Jicheng
Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, College of Life Sciences, Hubei Normal University, Huangshi 435002, China.
Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, College of Life Sciences, Hubei Normal University, Huangshi 435002, China.
Int J Biol Macromol. 2024 Dec;282(Pt 3):137002. doi: 10.1016/j.ijbiomac.2024.137002. Epub 2024 Oct 29.
Selenium nanoparticles (SeNPs) have limited bioavailability because of their poor stability in aqueous solutions. AAGL, a naturally active protein, extracted from Agrocybe aegerita has strong antitumor activity. However, whether AAGL can been used to stabilize SeNPs, and exerts anti-lung cancer effects remains unknown. In this study, a novel nanocomposite, AAGL-SeNPs, was prepared using AAGL-encapsulated SeNPs. The particle size of the AAGL-SeNPs was approximately 206.1 nm, which was uniform and well dispersed in aqueous solution and showed satisfactory stability. AAGL-SeNPs was non-toxic and reduced the hepatotoxicity of AAGL in mice. Importantly, AAGL-SeNPs inhibited the proliferation of lung cancer cells and suppressed tumor growth in tumor-bearing mice. AAGL-SeNPs enhanced the cytotoxic effects on lung cancer cells by stimulating immune cells. In addition, the combination of AAGL-SeNPs and osimertinib inhibited lung cancer, and AAGL-SeNPs reversed osimertinib resistance in H1975 cells. Mechanistically, Krüppel-like transcriptional factor 4 (KLF4) was identified by data-independent acquisition mass spectrometry (DIA-MS), and its expression levels in lung cancer increased after AAGL-SeNPs treatment. This study demonstrated that nanocomposite AAGL-SeNPs is stable, safe, and has excellent antitumor efficacy, which will be a potential therapeutic drug for lung cancer treatment.
由于硒纳米颗粒（SeNPs）在水溶液中的稳定性较差，其生物利用度有限。从高大环柄菇中提取的天然活性蛋白AAGL具有很强的抗肿瘤活性。然而，AAGL是否可用于稳定SeNPs并发挥抗肺癌作用尚不清楚。在本研究中，使用包裹AAGL的SeNPs制备了一种新型纳米复合材料AAGL-SeNPs。AAGL-SeNPs的粒径约为206.1nm，粒径均匀，在水溶液中分散良好，稳定性令人满意。AAGL-SeNPs无毒，并降低了AAGL对小鼠的肝毒性。重要的是，AAGL-SeNPs抑制肺癌细胞的增殖，并抑制荷瘤小鼠的肿瘤生长。AAGL-SeNPs通过刺激免疫细胞增强对肺癌细胞的细胞毒性作用。此外，AAGL-SeNPs与奥希替尼联合使用可抑制肺癌，并且AAGL-SeNPs可逆转H1975细胞对奥希替尼的耐药性。从机制上讲，通过数据非依赖采集质谱（DIA-MS）鉴定出Krüppel样转录因子4（KLF4），在AAGL-SeNPs处理后，其在肺癌中的表达水平升高。本研究表明，纳米复合材料AAGL-SeNPs稳定、安全，具有优异的抗肿瘤疗效，将成为肺癌治疗的潜在治疗药物。
