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ACS Appl Mater Interfaces ; 12(12): 13657-13670, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32091877

RESUMO

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.


Assuntos
Membrana Celular/efeitos dos fármacos , Eucariotos/efeitos dos fármacos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Animais , Bactérias/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Membrana Celular/química , Humanos , Luz , Camundongos , Nanoestruturas/efeitos da radiação , Nanoestruturas/uso terapêutico
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