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1.
Theranostics ; 7(13): 3326-3337, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28900513

RESUMEN

Biomedical applications of magnetic nanoparticles under the influence of a magnetic field have been proved useful beyond expectations in cancer therapy. Magnetic nanoparticles are effective heat mediators, drug nanocarriers, and contrast agents; various strategies have been suggested to selectively target tumor cancer cells. Our study presents magnetodynamic nanotherapy using DNA aptamer-functionalized 50 nm gold-coated magnetic nanoparticles exposed to a low frequency alternating magnetic field for selective elimination of tumor cells in vivo. The cell specific DNA aptamer AS-14 binds to the fibronectin protein in Ehrlich carcinoma hence helps deliver the gold-coated magnetic nanoparticles to the mouse tumor. Applying an alternating magnetic field of 50 Hz at the tumor site causes the nanoparticles to oscillate and pull the fibronectin proteins and integrins to the surface of the cell membrane. This results in apoptosis followed by necrosis of tumor cells without heating the tumor, adjacent healthy cells and tissues. The aptamer-guided nanoparticles and the low frequency alternating magnetic field demonstrates a unique non-invasive nanoscalpel technology for precise cancer surgery at the single cell level.


Asunto(s)
Aptámeros de Nucleótidos/química , Oro/química , Campos Magnéticos , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Animales , Apoptosis , Caspasas/metabolismo , Línea Celular Tumoral , Femenino , Masculino , Ratones Endogámicos ICR , Neoplasias/sangre , Neoplasias/patología , Neoplasias/terapia
2.
Mol Ther Nucleic Acids ; 6: 150-162, 2017 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-28325282

RESUMEN

Nucleic acid aptamers are becoming popular as molecular probes for identification and imaging pathology and, at the same time, as a convenient platform for targeted therapy. Recent studies have shown that aptamers may be effectively used for tumor characterization and as commercially available monoclonal antibodies. Here we present three DNA aptamers binding to whole transformed lung cancer tissues, including tumor cells, connective tissues, and blood vessels. Protein targets have been revealed using affinity purification followed by mass spectrometry analyses, and they have been validated using a panel of correspondent antibodies and 3D imaging of tumor tissues. Each of the proteins targeted by the aptamers is involved in cancer progression and most of them are crucial for lung adenocarcinoma. We propose the use of these aptamers in aptahistochemistry for the characterization of the histological structure of lung adenocarcinoma. The value of the presented aptamers is their application together or separately for indicating the spread of neoplastic transformation, for complex differential diagnostics, and for targeted therapy of the tumor itself as well as all transformed structures of the adjacent tissues. Moreover, it has been demonstrated that these aptamers could be used for intraoperative tumor visualization and margin assessment.

3.
Nucleic Acid Ther ; 27(2): 105-114, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27923103

RESUMEN

Magnetomechanical cell disruption using nano- and microsized structures is a promising biomedical technology used for noninvasive elimination of diseased cells. It applies alternating magnetic field (AMF) for ferromagnetic microdisks making them oscillate and causing cell membrane disruption with cell death followed by apoptosis. In this study, we functionalized the magnetic microdisks with cell-binding DNA aptamers and guided the microdisks to recognize cancerous cells in a mouse tumor in vivo. Only 10 min of the treatment with a 100 Hz AMF was enough to eliminate cancer cells from a malignant tumor. Our results demonstrate a good perspective of using aptamer-modified magnetic microdisks for noninvasive microsurgery for tumors.


Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Carcinoma de Ehrlich/terapia , Magnetoterapia/métodos , Campos Magnéticos , Microcirugia/métodos , Animales , Aptámeros de Nucleótidos/síntesis química , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patología , Fibronectinas/metabolismo , Filaminas/metabolismo , Inyecciones Intralesiones , Magnetoterapia/instrumentación , Imanes , Masculino , Ratones , Ratones Endogámicos ICR , Trasplante de Neoplasias , Unión Proteica , Compuestos de Sulfhidrilo/química
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