Molecular Nanomachines Can Destroy Tissue or Kill Multicellular Eukaryotes.

Molecular Nanomachines Can Destroy Tissue or Kill Multicellular Eukaryotes.
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DOI:
10.1021/acsami.9b22595
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发表时间:
2020-03-25
影响因子:
9.5
通讯作者:
Tour JM
Tour JM
中科院分区:
材料科学2区
文献类型:
--
作者:
Gunasekera RS;Galbadage T;Ayala-Orozco C;Liu D;García-López V;Troutman BE;Tour JJ;Pal R;Krishnan S;Cirillo JD;Tour JM

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光激活的分子纳米机器可以通过快速的旋转运动在原核(细菌)细胞壁和包括哺乳动物癌细胞在内的真核细胞的细胞膜上钻孔,导致细胞死亡。我们研究了这些MNMs如何在多细胞生物体中发挥作用,并调查了它们通过对某些组织和小生物造成损害而用于治疗和根除特定疾病的情况。评价了三种模式真核生物:秀丽线虫、普氏水蚤和小鼠。将这些生物暴露在光激活的快速旋转的MNMs中,并对其生理和病理变化进行了详细的研究。用慢速旋转的MNM控制转速的影响。我们证明,快速旋转的MNMS导致线虫脱色和70%的死亡,同时减缓了运动和心率,并导致了水蚤的组织损伤。在小鼠皮肤上局部应用光激活的MNMS会导致皮肤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。总体而言,这项研究表明,光激活的MNMs的纳米机械作用对体内的多细胞生物体有效,破坏细胞膜和破坏组织。针对特定组织进行治疗并结合时间和空间控制的定制MNMs可在多种良性和恶性疾病状态下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。
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, Caenorhabditis elegans, Daphnia pulex, and Mus musculus (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 C. elegans while reducing the movement as well as heart rate and causing tissue damage in Daphnia. 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 in vivo. 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.
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