Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment

Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment

Vanna Sanna,1,2 Jean Christopher Chamcheu,3 Nicolino Pala,1 Hasan Mukhtar,3 Mario Sechi,1,2 Imtiaz Ahmad Siddiqui3 1Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; 2Laboratory of Nanomedicine, University of Sassari, Sassari, Italy; 3Department of Dermatology, University...

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Autores principales: Sanna V, Chamcheu JC, Pala N, Mukhtar H, Sechi M, Siddiqui IA
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5ab718b207424643b3d201ab896db9db
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spelling oai:doaj.org-article:5ab718b207424643b3d201ab896db9db2021-12-02T01:07:47ZNanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment1178-2013https://doaj.org/article/5ab718b207424643b3d201ab896db9db2015-10-01T00:00:00Zhttps://www.dovepress.com/nanoencapsulation-of-natural-triterpenoid-celastrol-for-prostate-cance-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Vanna Sanna,1,2 Jean Christopher Chamcheu,3 Nicolino Pala,1 Hasan Mukhtar,3 Mario Sechi,1,2 Imtiaz Ahmad Siddiqui3 1Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; 2Laboratory of Nanomedicine, University of Sassari, Sassari, Italy; 3Department of Dermatology, University of Wisconsin, Madison, WI, USA Abstract: Celastrol (CL), a triterpenoid extracted from the Chinese herb Tripterygium wilfordii, has recently attracted interest for its potential antitumor effects. However, unfavorable physicochemical and pharmacokinetics properties such as low solubility, poor bioavailability, and systemic toxicity, are limiting its therapeutic application. In this context, the development of innovative nanocarriers can be useful to overcome these issues, and nanoencapsulation would represent a powerful strategy. In this study, we developed novel CL-loaded poly(ε-caprolactone) nanoparticles (NPs), and investigated their antiproliferative efficacy on prostate cancer cells. CL-NPs were prepared using a nanoprecipitation method and fully characterized by physicochemical techniques. The antiproliferative effects on LNCaP, DU-145, and PC3 cell lines of CL-NPs, compared to those of free CL at different concentrations (0.5, 1.0, and 2.0 µM), were investigated. Moreover, fluorescence microscopy was utilized to examine the cellular uptake of the nanosystems. Furthermore, to elucidate impact of nanoencapsulation on the mechanism of action, Western analyses were conducted to explore apoptosis, migration, proliferation, and angiogenesis alteration of prostate cancer cells. The results confirmed that CL-NPs inhibit proliferation dose dependently in all prostate cancer cells, with inhibitory concentration50 less than 2 µM. In particular, the NPs significantly increased cytotoxicity at lower/medium dose (0.5 and 1.0 µM) on DU145 and PC3 cell lines with respect to free CL, with modulation of apoptotic and cell cycle machinery proteins. To date, this represents the first report on the development of biocompatible polymeric NPs encapsulating CL. Our findings offer new perspectives for the exploitation of developed CL-NPs as suitable prototypes for prostate cancer treatment. Keywords: celastrol, tripterine, nanoparticles, poly(ε-caprolactone), prostate cancerSanna VChamcheu JCPala NMukhtar HSechi MSiddiqui IADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6835-6846 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Sanna V
Chamcheu JC
Pala N
Mukhtar H
Sechi M
Siddiqui IA
Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
description Vanna Sanna,1,2 Jean Christopher Chamcheu,3 Nicolino Pala,1 Hasan Mukhtar,3 Mario Sechi,1,2 Imtiaz Ahmad Siddiqui3 1Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; 2Laboratory of Nanomedicine, University of Sassari, Sassari, Italy; 3Department of Dermatology, University of Wisconsin, Madison, WI, USA Abstract: Celastrol (CL), a triterpenoid extracted from the Chinese herb Tripterygium wilfordii, has recently attracted interest for its potential antitumor effects. However, unfavorable physicochemical and pharmacokinetics properties such as low solubility, poor bioavailability, and systemic toxicity, are limiting its therapeutic application. In this context, the development of innovative nanocarriers can be useful to overcome these issues, and nanoencapsulation would represent a powerful strategy. In this study, we developed novel CL-loaded poly(ε-caprolactone) nanoparticles (NPs), and investigated their antiproliferative efficacy on prostate cancer cells. CL-NPs were prepared using a nanoprecipitation method and fully characterized by physicochemical techniques. The antiproliferative effects on LNCaP, DU-145, and PC3 cell lines of CL-NPs, compared to those of free CL at different concentrations (0.5, 1.0, and 2.0 µM), were investigated. Moreover, fluorescence microscopy was utilized to examine the cellular uptake of the nanosystems. Furthermore, to elucidate impact of nanoencapsulation on the mechanism of action, Western analyses were conducted to explore apoptosis, migration, proliferation, and angiogenesis alteration of prostate cancer cells. The results confirmed that CL-NPs inhibit proliferation dose dependently in all prostate cancer cells, with inhibitory concentration50 less than 2 µM. In particular, the NPs significantly increased cytotoxicity at lower/medium dose (0.5 and 1.0 µM) on DU145 and PC3 cell lines with respect to free CL, with modulation of apoptotic and cell cycle machinery proteins. To date, this represents the first report on the development of biocompatible polymeric NPs encapsulating CL. Our findings offer new perspectives for the exploitation of developed CL-NPs as suitable prototypes for prostate cancer treatment. Keywords: celastrol, tripterine, nanoparticles, poly(ε-caprolactone), prostate cancer
format article
author Sanna V
Chamcheu JC
Pala N
Mukhtar H
Sechi M
Siddiqui IA
author_facet Sanna V
Chamcheu JC
Pala N
Mukhtar H
Sechi M
Siddiqui IA
author_sort Sanna V
title Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
title_short Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
title_full Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
title_fullStr Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
title_full_unstemmed Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
title_sort nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/5ab718b207424643b3d201ab896db9db
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