Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of...

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Autores principales:	Shan L, Liu M, Wu C, Zhao L, Li S, Xu L, Cao W, Gao G, Gu Y
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Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/01b1b0d30e2e4753bf054398de13e95e
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spelling	oai:doaj.org-article:01b1b0d30e2e4753bf054398de13e95e2021-12-02T03:05:08ZMulti-small molecule conjugations as new targeted delivery carriers for tumor therapy1178-2013https://doaj.org/article/01b1b0d30e2e4753bf054398de13e95e2015-09-01T00:00:00Zhttp://www.dovepress.com/multi-small-molecule-conjugations-as-new-targeted-delivery-carriers-fo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX) as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6)-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX) and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX), composed of folic acid (FA, target), amino acids (Arg or Glu, linker), and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo) in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapyShan LLiu MWu CZhao LLi SXu LCao WGao GGu YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5571-5591 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shan L Liu M Wu C Zhao L Li S Xu L Cao W Gao G Gu Y Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
description	Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX) as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6)-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX) and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX), composed of folic acid (FA, target), amino acids (Arg or Glu, linker), and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo) in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy
format	article
author	Shan L Liu M Wu C Zhao L Li S Xu L Cao W Gao G Gu Y
author_facet	Shan L Liu M Wu C Zhao L Li S Xu L Cao W Gao G Gu Y
author_sort	Shan L
title	Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
title_short	Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
title_full	Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
title_fullStr	Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
title_full_unstemmed	Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
title_sort	multi-small molecule conjugations as new targeted delivery carriers for tumor therapy
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/01b1b0d30e2e4753bf054398de13e95e
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Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

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