Lunova Mariia, Smolková Barbora, Lynnyk Anna, Uzhytchak Mariia, Jirsa Milan, Kubinová Šárka, Dejneka Alexandr, Lunov Oleg
Institute of Physics of the Czech Academy of Sciences, Prague, 18221, Czech Republic.
Institute for Clinical & Experimental Medicine (IKEM), Prague, 140 21, Czech Republic.
Cancers (Basel). 2019 Jan 11;11(1):82. doi: 10.3390/cancers11010082.
Proteins of the mammalian target of rapamycin (mTOR) signaling axis are overexpressed or mutated in cancers. However, clinical inhibition of mTOR signaling as a therapeutic strategy in oncology shows rather limited progress. Nanoparticle-based mTOR targeted therapy proposes an attractive therapeutic option for various types of cancers. Along with the progress in the biomedical applications of nanoparticles, we start to realize the challenges and opportunities that lie ahead. Here, we critically analyze the current literature on the modulation of mTOR activity by nanoparticles, demonstrate the complexity of cellular responses to functionalized nanoparticles, and underline challenges lying in the identification of the molecular mechanisms of mTOR signaling affected by nanoparticles. We propose the idea that subcytotoxic doses of nanoparticles could be relevant for the induction of subcellular structural changes with possible involvement of mTORC1 signaling. The evaluation of the mechanisms and therapeutic effects of nanoparticle-based mTOR modulation will provide fundamental knowledge which could help in developing safe and efficient nano-therapeutics.
哺乳动物雷帕霉素靶蛋白（mTOR）信号轴的蛋白质在癌症中过表达或发生突变。然而，作为肿瘤学治疗策略的mTOR信号临床抑制进展相当有限。基于纳米颗粒的mTOR靶向治疗为各类癌症提供了一种有吸引力的治疗选择。随着纳米颗粒在生物医学应用方面的进展，我们开始意识到未来面临的挑战和机遇。在此，我们批判性地分析了当前关于纳米颗粒调节mTOR活性的文献，展示了细胞对功能化纳米颗粒反应的复杂性，并强调了在确定受纳米颗粒影响的mTOR信号分子机制方面存在的挑战。我们提出，亚细胞毒性剂量的纳米颗粒可能与诱导亚细胞结构变化有关，mTORC1信号可能参与其中。对基于纳米颗粒的mTOR调节机制和治疗效果的评估将提供基础知识，有助于开发安全有效的纳米治疗方法。
