Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas 77807, United States.
Department of Experimental Oncology, MD Anderson Cancer Center, Houston, Texas 77030, United States.
ACS Appl Mater Interfaces. 2020 Mar 25;12(12):13657-13670. doi: 10.1021/acsami.9b22595. Epub 2020 Mar 13.
Light-activated molecular nanomachines (MNMs) can be used to drill holes into prokaryotic (bacterial) cell walls and the membrane of eukaryotic cells, including mammalian cancer cells, by their fast rotational movement, leading to cell death. We examined how these MNMs function in multicellular organisms and investigated their use for treatment and eradication of specific diseases by causing damage to certain tissues and small organisms. Three model eukaryotic species, , , and (mouse), were evaluated. These organisms were exposed to light-activated fast-rotating MNMs and their physiological and pathological changes were studied in detail. Slow rotating MNMs were used to control for the effects of rotation rate. We demonstrate that fast-rotating MNMs caused depigmentation and 70% mortality in while reducing the movement as well as heart rate and causing tissue damage in . Topically applied light-activated MNMs on mouse skin caused ulceration and microlesions in the epithelial tissue, allowing MNMs to localize into deeper epidermal tissue. Overall, this study shows that the nanomechanical action of light-activated MNMs is effective against multicellular organisms, disrupting cell membranes and damaging tissue . Customized MNMs that target specific tissues for therapy combined with spatial and temporal control could have broad clinical applications in a variety of benign and malignant disease states including treatment of cancer, parasites, bacteria, and diseased tissues.
光激活的分子纳米机器(MNMs)可以通过快速旋转运动钻入原核(细菌)细胞壁和真核细胞的膜,包括哺乳动物癌细胞,导致细胞死亡。我们研究了这些 MNMs 在多细胞生物中的作用,并研究了它们通过对特定组织和小生物体造成损伤来用于治疗和消除特定疾病的用途。评估了三个模型真核生物物种、、和(小鼠)。这些生物体暴露于光激活的快速旋转 MNMs 下,并详细研究了它们的生理和病理变化。使用缓慢旋转的 MNMs 来控制旋转速度的影响。我们证明,快速旋转的 MNMs 导致白化和 70%的死亡率,而减少运动以及心率,并导致组织损伤。在小鼠皮肤上局部应用光激活的 MNMs 会导致上皮组织的溃疡和微损伤,使 MNMs 能够定位到更深的表皮组织中。总的来说,这项研究表明,光激活的 MNMs 的纳米机械作用对多细胞生物有效,破坏细胞膜并损伤组织。针对特定组织进行治疗的定制 MNMs 与时空控制相结合,可能在各种良性和恶性疾病状态中具有广泛的临床应用,包括癌症、寄生虫、细菌和病变组织的治疗。