Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells

For cells and tissues, cell–cell and cell–extracellular matrix adhesion is important for proliferation, differentiation, and response to mechanical stimuli. This adhesion is provided by various cell adhesion molecules (CAMs). However, in breast cancer, depending upon the type and stage, this adheren...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maeirah Ashaie, Ezharul Hoque Chowdhury
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cell adhesion molecules (CAM) integrins siRNAs carbonate apatite (CA) nanoparticles Technology T Engineering (General). Civil engineering (General) TA1-2040 Biology (General) QH301-705.5 Physics QC1-999 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/af99a658c33449d0bdda0aab07d732d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:af99a658c33449d0bdda0aab07d732d1
record_format	dspace
spelling	oai:doaj.org-article:af99a658c33449d0bdda0aab07d732d12021-11-25T16:37:58ZNanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells10.3390/app1122107822076-3417https://doaj.org/article/af99a658c33449d0bdda0aab07d732d12021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3417/11/22/10782https://doaj.org/toc/2076-3417For cells and tissues, cell–cell and cell–extracellular matrix adhesion is important for proliferation, differentiation, and response to mechanical stimuli. This adhesion is provided by various cell adhesion molecules (CAMs). However, in breast cancer, depending upon the type and stage, this adherence is dysregulated where the expression of these cell adhesion molecules is either overregulated or unregulated, triggering essential oncogenic pathways. Thus, to control the invasiveness of tumor cells, and reduce metastasis, regulating the homophilic and heterophilic interaction of these molecules and controlling the essential cell pathways is important. In this study, we targeted critical CAMs- integrins to regulate their aberrated behavior via siRNAs delivery. However, as due to charge repulsion and propensity to be degraded by nucleases prior to reaching the target site, naked siRNAs are unable to cross plasma membrane, use of a suitable carrier vehicle is essential. Thus, we employed carbonate apatite (CA), to deliver the selected siRNAs targeting integrin αv, α6, β1, β3, β4, β5, and β6 subunits to various breast cancer cell lines and 4T1-breast cancer induced murine model. Delivery of individual integrin siRNAs complexed with CA nanoparticles (NPs) reduced cell viability and caused decrease in tumor burden. To check the gene knockdown effects on phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and extracellular signal–regulated kinases/mitogen-activated protein kinase (ERK/MAPK) pathways, Western blot analysis was performed, revealing downregulation of the signaling molecules. Thus, CA-facilitated gene therapy targeting various integrins could poise potential therapeutic modality against breast cancer.Maeirah AshaieEzharul Hoque ChowdhuryMDPI AGarticlecell adhesion molecules (CAM)integrinssiRNAscarbonate apatite (CA)nanoparticlesTechnologyTEngineering (General). Civil engineering (General)TA1-2040Biology (General)QH301-705.5PhysicsQC1-999ChemistryQD1-999ENApplied Sciences, Vol 11, Iss 10782, p 10782 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell adhesion molecules (CAM) integrins siRNAs carbonate apatite (CA) nanoparticles Technology T Engineering (General). Civil engineering (General) TA1-2040 Biology (General) QH301-705.5 Physics QC1-999 Chemistry QD1-999
spellingShingle	cell adhesion molecules (CAM) integrins siRNAs carbonate apatite (CA) nanoparticles Technology T Engineering (General). Civil engineering (General) TA1-2040 Biology (General) QH301-705.5 Physics QC1-999 Chemistry QD1-999 Maeirah Ashaie Ezharul Hoque Chowdhury Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
description	For cells and tissues, cell–cell and cell–extracellular matrix adhesion is important for proliferation, differentiation, and response to mechanical stimuli. This adhesion is provided by various cell adhesion molecules (CAMs). However, in breast cancer, depending upon the type and stage, this adherence is dysregulated where the expression of these cell adhesion molecules is either overregulated or unregulated, triggering essential oncogenic pathways. Thus, to control the invasiveness of tumor cells, and reduce metastasis, regulating the homophilic and heterophilic interaction of these molecules and controlling the essential cell pathways is important. In this study, we targeted critical CAMs- integrins to regulate their aberrated behavior via siRNAs delivery. However, as due to charge repulsion and propensity to be degraded by nucleases prior to reaching the target site, naked siRNAs are unable to cross plasma membrane, use of a suitable carrier vehicle is essential. Thus, we employed carbonate apatite (CA), to deliver the selected siRNAs targeting integrin αv, α6, β1, β3, β4, β5, and β6 subunits to various breast cancer cell lines and 4T1-breast cancer induced murine model. Delivery of individual integrin siRNAs complexed with CA nanoparticles (NPs) reduced cell viability and caused decrease in tumor burden. To check the gene knockdown effects on phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and extracellular signal–regulated kinases/mitogen-activated protein kinase (ERK/MAPK) pathways, Western blot analysis was performed, revealing downregulation of the signaling molecules. Thus, CA-facilitated gene therapy targeting various integrins could poise potential therapeutic modality against breast cancer.
format	article
author	Maeirah Ashaie Ezharul Hoque Chowdhury
author_facet	Maeirah Ashaie Ezharul Hoque Chowdhury
author_sort	Maeirah Ashaie
title	Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
title_short	Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
title_full	Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
title_fullStr	Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
title_full_unstemmed	Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
title_sort	nanoparticles-facilitated intracellular transport of sirnas against individual integrin subunits inhibits growth of breast cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/af99a658c33449d0bdda0aab07d732d1
work_keys_str_mv	AT maeirahashaie nanoparticlesfacilitatedintracellulartransportofsirnasagainstindividualintegrinsubunitsinhibitsgrowthofbreastcancercells AT ezharulhoquechowdhury nanoparticlesfacilitatedintracellulartransportofsirnasagainstindividualintegrinsubunitsinhibitsgrowthofbreastcancercells
_version_	1718413096690647040

Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells

Ejemplares similares