Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells

Prajakta Tambe,1,2,* Pramod Kumar,1,2,* Kishore M Paknikar,1,2 Virendra Gajbhiye1,2 1Nanobioscience Group, Agharkar Research Institute, Pune, India; 2Savitribai Phule Pune University, Pune, India *These authors contributed equally to this work Background: Considering the increase in cancer cases...

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Autores principales:	Tambe P, Kumar P, Paknikar KM, Gajbhiye V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Mesoporous silica nanoparticles GnRH receptors Receptor-mediated endocytosis Breast and prostate cancer Decapeptide Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b687514630024bd78dc934c6c4a933f0
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spelling	oai:doaj.org-article:b687514630024bd78dc934c6c4a933f02021-12-02T07:13:02ZDecapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells1178-2013https://doaj.org/article/b687514630024bd78dc934c6c4a933f02018-11-01T00:00:00Zhttps://www.dovepress.com/decapeptide-functionalized-targeted-mesoporous-silica-nanoparticles-wi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Prajakta Tambe,1,2,* Pramod Kumar,1,2,* Kishore M Paknikar,1,2 Virendra Gajbhiye1,2 1Nanobioscience Group, Agharkar Research Institute, Pune, India; 2Savitribai Phule Pune University, Pune, India *These authors contributed equally to this work Background: Considering the increase in cancer cases and number of deaths per year worldwide, development of potential therapeutics is imperative. Mesoporous silica nanoparticles (MSNPs) are among the potential nanocarriers having unique properties for drug delivery. Doxorubicin (DOX), being the most commonly used drug, can be efficiently delivered to gonadotropin-releasing hormone (GnRH)-overexpressing cancer cells using functionalized MSNPs.Aim: We report the development of decapeptide-conjugated MSNPs loaded with DOX for the targeted drug delivery in breast and prostate cancer cells.Materials and methods: MSNPs were synthesized and subsequently functionalized with an analog of GnRH by using a heterobifunctional polyethylene glycol as a linker. These targeted MSNPs were then characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. An anticancer drug DOX was loaded and then characterized for drug loading. DOX-loaded nanocarriers were then studied for their cellular uptake using confocal microscopy. The cytotoxicity of DOX-loaded targeted MSNPs and DOX-loaded bare MSNPs was studied by performing MTT assay on MCF-7 (breast cancer) and LNCaP (prostate cancer) cells. Further, acridine orange/ethidium bromide staining, as well as flow cytometry, was performed to confirm the apoptotic mode of cancer cell death.Results: MSNPs were conjugated with polyethylene glycol as well as an agonist of GnRH and subsequently loaded with DOX. These targeted and bare MSNPs showed excellent porous structure and loading of DOX. Further, higher uptake of DOX-loaded targeted MSNPs was observed as compared to DOX-loaded bare MSNPs in GnRH-overexpressing breast (MCF-7) and prostate (LNCaP) cancer cells. The targeted MSNPs also showed significantly higher (P<0.001) cytotoxicity than DOX-loaded bare MSNPs at different time points. After 48 hours of treatment, the IC50 value for DOX-loaded targeted MSNPs was found to be 0.44 and 0.43 µM in MCF-7 and LNCaP cells, respectively. Acridine orange/ethidium bromide staining and flow cytometry analysis further confirmed the pathway of cell death through apoptosis.Conclusion: This study suggests GnRH analog-conjugated targeted MSNPs can be the suitable and promising approach for targeted drug delivery in all hormone-dependent cancer cells. Keywords: mesoporous silica nanoparticles, GnRH receptors, receptor-mediated endocytosis, breast and prostate cancer, decapeptide Tambe PKumar PPaknikar KMGajbhiye VDove Medical PressarticleMesoporous silica nanoparticlesGnRH receptorsReceptor-mediated endocytosisBreast and prostate cancerDecapeptideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7669-7680 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesoporous silica nanoparticles GnRH receptors Receptor-mediated endocytosis Breast and prostate cancer Decapeptide Medicine (General) R5-920
spellingShingle	Mesoporous silica nanoparticles GnRH receptors Receptor-mediated endocytosis Breast and prostate cancer Decapeptide Medicine (General) R5-920 Tambe P Kumar P Paknikar KM Gajbhiye V Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
description	Prajakta Tambe,1,2,* Pramod Kumar,1,2,* Kishore M Paknikar,1,2 Virendra Gajbhiye1,2 1Nanobioscience Group, Agharkar Research Institute, Pune, India; 2Savitribai Phule Pune University, Pune, India *These authors contributed equally to this work Background: Considering the increase in cancer cases and number of deaths per year worldwide, development of potential therapeutics is imperative. Mesoporous silica nanoparticles (MSNPs) are among the potential nanocarriers having unique properties for drug delivery. Doxorubicin (DOX), being the most commonly used drug, can be efficiently delivered to gonadotropin-releasing hormone (GnRH)-overexpressing cancer cells using functionalized MSNPs.Aim: We report the development of decapeptide-conjugated MSNPs loaded with DOX for the targeted drug delivery in breast and prostate cancer cells.Materials and methods: MSNPs were synthesized and subsequently functionalized with an analog of GnRH by using a heterobifunctional polyethylene glycol as a linker. These targeted MSNPs were then characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. An anticancer drug DOX was loaded and then characterized for drug loading. DOX-loaded nanocarriers were then studied for their cellular uptake using confocal microscopy. The cytotoxicity of DOX-loaded targeted MSNPs and DOX-loaded bare MSNPs was studied by performing MTT assay on MCF-7 (breast cancer) and LNCaP (prostate cancer) cells. Further, acridine orange/ethidium bromide staining, as well as flow cytometry, was performed to confirm the apoptotic mode of cancer cell death.Results: MSNPs were conjugated with polyethylene glycol as well as an agonist of GnRH and subsequently loaded with DOX. These targeted and bare MSNPs showed excellent porous structure and loading of DOX. Further, higher uptake of DOX-loaded targeted MSNPs was observed as compared to DOX-loaded bare MSNPs in GnRH-overexpressing breast (MCF-7) and prostate (LNCaP) cancer cells. The targeted MSNPs also showed significantly higher (P<0.001) cytotoxicity than DOX-loaded bare MSNPs at different time points. After 48 hours of treatment, the IC50 value for DOX-loaded targeted MSNPs was found to be 0.44 and 0.43 µM in MCF-7 and LNCaP cells, respectively. Acridine orange/ethidium bromide staining and flow cytometry analysis further confirmed the pathway of cell death through apoptosis.Conclusion: This study suggests GnRH analog-conjugated targeted MSNPs can be the suitable and promising approach for targeted drug delivery in all hormone-dependent cancer cells. Keywords: mesoporous silica nanoparticles, GnRH receptors, receptor-mediated endocytosis, breast and prostate cancer, decapeptide
format	article
author	Tambe P Kumar P Paknikar KM Gajbhiye V
author_facet	Tambe P Kumar P Paknikar KM Gajbhiye V
author_sort	Tambe P
title	Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
title_short	Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
title_full	Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
title_fullStr	Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
title_full_unstemmed	Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
title_sort	decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b687514630024bd78dc934c6c4a933f0
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Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells

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