Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy

Mengen Zhang1,2, Rui Guo2, Yin Wang2, Xueyan Cao2, Mingwu Shen2, Xiangyang Shi1-31State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3Ce...

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Autores principales: Zhang M, Guo R, Wang Y, Cao X, Shen M, Shi X
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Publicado: Dove Medical Press 2011
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spelling oai:doaj.org-article:baba3bf5e50149138248c51561d176122021-12-02T01:19:12ZMultifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy1176-91141178-2013https://doaj.org/article/baba3bf5e50149138248c51561d176122011-10-01T00:00:00Zhttp://www.dovepress.com/multifunctional-dendrimercombretastatin-a4-inclusion-complexes-enable--a8478https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Mengen Zhang1,2, Rui Guo2, Yin Wang2, Xueyan Cao2, Mingwu Shen2, Xiangyang Shi1-31State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, PortugalBackground: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics.Methods: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors.Results: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 µg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors.Conclusion: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.Keywords: PAMAM dendrimers, combretastatin A4, inclusion complexes, targeted cancer therapyZhang MGuo RWang YCao XShen MShi XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2337-2349 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Zhang M
Guo R
Wang Y
Cao X
Shen M
Shi X
Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
description Mengen Zhang1,2, Rui Guo2, Yin Wang2, Xueyan Cao2, Mingwu Shen2, Xiangyang Shi1-31State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, PortugalBackground: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics.Methods: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors.Results: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 µg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors.Conclusion: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.Keywords: PAMAM dendrimers, combretastatin A4, inclusion complexes, targeted cancer therapy
format article
author Zhang M
Guo R
Wang Y
Cao X
Shen M
Shi X
author_facet Zhang M
Guo R
Wang Y
Cao X
Shen M
Shi X
author_sort Zhang M
title Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
title_short Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
title_full Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
title_fullStr Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
title_full_unstemmed Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy
title_sort multifunctional dendrimer/combretastatin a4 inclusion complexes enable in vitro targeted cancer therapy
publisher Dove Medical Press
publishDate 2011
url https://doaj.org/article/baba3bf5e50149138248c51561d17612
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