MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer

Abstract RNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Byunghee Yoo, Alana Ross, Pamela Pantazopoulos, Zdravka Medarova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aba3c435f7b44d53a08fc458de111e51
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aba3c435f7b44d53a08fc458de111e51
record_format	dspace
spelling	oai:doaj.org-article:aba3c435f7b44d53a08fc458de111e512021-12-02T14:06:24ZMiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer10.1038/s41598-021-82528-22045-2322https://doaj.org/article/aba3c435f7b44d53a08fc458de111e512021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82528-2https://doaj.org/toc/2045-2322Abstract RNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.Byunghee YooAlana RossPamela PantazopoulosZdravka MedarovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Byunghee Yoo Alana Ross Pamela Pantazopoulos Zdravka Medarova MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
description	Abstract RNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.
format	article
author	Byunghee Yoo Alana Ross Pamela Pantazopoulos Zdravka Medarova
author_facet	Byunghee Yoo Alana Ross Pamela Pantazopoulos Zdravka Medarova
author_sort	Byunghee Yoo
title	MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
title_short	MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
title_full	MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
title_fullStr	MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
title_full_unstemmed	MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer
title_sort	mirna10b-directed nanotherapy effectively targets brain metastases from breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aba3c435f7b44d53a08fc458de111e51
work_keys_str_mv	AT byungheeyoo mirna10bdirectednanotherapyeffectivelytargetsbrainmetastasesfrombreastcancer AT alanaross mirna10bdirectednanotherapyeffectivelytargetsbrainmetastasesfrombreastcancer AT pamelapantazopoulos mirna10bdirectednanotherapyeffectivelytargetsbrainmetastasesfrombreastcancer AT zdravkamedarova mirna10bdirectednanotherapyeffectivelytargetsbrainmetastasesfrombreastcancer
_version_	1718392041591799808

MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer

Ejemplares similares