Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment

Authors Sanna V, Chamcheu JC, Pala N, Mukhtar H, Sechi M, Siddiqui IA

Received 6 August 2015

Accepted for publication 26 September 2015

Published 30 October 2015 Volume 2015:10(1) Pages 6835—6846

DOI https://doi.org/10.2147/IJN.S93752

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Optimal delivery of male breast cancer follow-up care: improving outcomes

Ferzoco RM, Ruddy KJ

Breast Cancer: Targets and Therapy 2015, 7:371-379

Published Date: 23 November 2015

Advances in cancer pain from bone metastasis

Zhu XC, Zhang JL, Ge CT, Yu YY, Wang P, Yuan TF, Fu CY

Drug Design, Development and Therapy 2015, 9:4239-4245

Published Date: 18 August 2015

The role of regulatory T cells in cancer immunology

Whiteside TL

ImmunoTargets and Therapy 2015, 4:159-171

Published Date: 5 August 2015

The potential clinical applications and prospects of microRNAs in lung cancer

Gao Y, Gao F, Ma JL, Sun WZ, Song LP

OncoTargets and Therapy 2014, 7:901-906

Published Date: 4 June 2014

Update of research on the role of EZH2 in cancer progression

Shen L, Cui J, Liang S, Pang Y, Liu P

OncoTargets and Therapy 2013, 6:321-324

Published Date: 4 April 2013