Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer

Bo Hu,1 Ying Yan,2 Fei Tong,1 Long Xu,1 Jia Zhu,1 Guangtao Xu,1 Ruilin Shen1 1Department of Oncopathology, Institute of Diabetes and Urological Disease, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 2Department of Rehabilitation Medicine, The Third Affiliated Hospit...

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Autores principales:	Hu B, Yan Y, Tong F, Xu L, Zhu J, Xu G, Shen R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	copolymer nanoparticles lumbrokinase paclitaxel bladder cancer microvessel density p53 cyclin B1 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1f16d12259294966b2dae454175e6d3f
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spelling	oai:doaj.org-article:1f16d12259294966b2dae454175e6d3f2021-12-02T07:58:54ZLumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer1178-2013https://doaj.org/article/1f16d12259294966b2dae454175e6d3f2018-06-01T00:00:00Zhttps://www.dovepress.com/lumbrokinasepaclitaxel-nanoparticle-complex-potential-therapeutic-appl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bo Hu,1 Ying Yan,2 Fei Tong,1 Long Xu,1 Jia Zhu,1 Guangtao Xu,1 Ruilin Shen1 1Department of Oncopathology, Institute of Diabetes and Urological Disease, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Background: Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. Methods and results: Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. Conclusion: We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits. Keywords: copolymer nanoparticles, lumbrokinase, paclitaxel, bladder cancer, microvessel density, p53, cyclin B1Hu BYan YTong FXu LZhu JXu GShen RDove Medical Pressarticlecopolymer nanoparticleslumbrokinasepaclitaxelbladder cancermicrovessel densityp53cyclin B1Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3625-3640 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	copolymer nanoparticles lumbrokinase paclitaxel bladder cancer microvessel density p53 cyclin B1 Medicine (General) R5-920
spellingShingle	copolymer nanoparticles lumbrokinase paclitaxel bladder cancer microvessel density p53 cyclin B1 Medicine (General) R5-920 Hu B Yan Y Tong F Xu L Zhu J Xu G Shen R Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
description	Bo Hu,1 Ying Yan,2 Fei Tong,1 Long Xu,1 Jia Zhu,1 Guangtao Xu,1 Ruilin Shen1 1Department of Oncopathology, Institute of Diabetes and Urological Disease, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Background: Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. Methods and results: Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. Conclusion: We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits. Keywords: copolymer nanoparticles, lumbrokinase, paclitaxel, bladder cancer, microvessel density, p53, cyclin B1
format	article
author	Hu B Yan Y Tong F Xu L Zhu J Xu G Shen R
author_facet	Hu B Yan Y Tong F Xu L Zhu J Xu G Shen R
author_sort	Hu B
title	Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
title_short	Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
title_full	Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
title_fullStr	Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
title_full_unstemmed	Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
title_sort	lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/1f16d12259294966b2dae454175e6d3f
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Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer

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