Issue 11, 2010
From the journal:

Soft Matter

Influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers

Xiangyang Shi,*ab   Inhan Lee,*c   Xisui Chen,d   Mingwu Shen,b   Shili Xiao,b   Meifang Zhu,a   James R. Baker, Jrd  and  Su He Wang*d  

* Corresponding authors

a State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, P. R. China
E-mail: xshi@dhu.edu.cn

b College of Chemistry, Chemical Engineering and Biotechnology, Shanghai, P. R. China

c miRcore, Ann Arbor, MI, USA
E-mail: inhanlee99@gmail.com

d Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI, USA
E-mail: shidasui@umich.edu

Abstract

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6–8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers. In vitro cell biological assays show that amine, hydroxyl, and acetamide-terminated G5 dendrimers with positive, slightly positive, and close to neutral surface charges, respectively are able to deliver 2-ME to inhibit cancer cell growth. In contrast, 2-ME complexed with carboxyl-terminated G5 dendrimers with negative surface charges does not show its inherent bioactivity. Further molecular dynamics simulation studies show that the compact structure of carboxylated G5 dendrimers complexed with 2-ME does not allow the release of the drug molecules even at a pH of 5.0, which is the typical pH value in lysosome. Our findings indicate that the surface modification of dendrimers with different charges is crucial for the development of formulations of various anticancer drugs for therapeutic applications.

Graphical abstract: Influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers

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Article information

DOI
https://doi.org/10.1039/B925274F
Article type
Paper
Submitted
02 Dec 2009
Accepted
12 Mar 2010
First published
29 Apr 2010

Soft Matter, 2010,6, 2539-2545

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Influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers

X. Shi, I. Lee, X. Chen, M. Shen, S. Xiao, M. Zhu, J. R. Baker and S. H. Wang, Soft Matter, 2010, 6, 2539 DOI: 10.1039/B925274F

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