Issue 47, 2011
From the journal:

Journal of Materials Chemistry

Linear polyethyleneimine-based charge-reversal nanoparticles for nuclear-targeted drug delivery

Zhuxian Zhou,b   Youqing Shen,*a   Jianbin Tang,a   Erlei Jin,b   Xinpeng Ma,b   Qihang Sun,b   Bo Zhang,b   Edward A. Van Kirkc  and  William J. Murdochc  

* Corresponding authors

a Center for Bionanoengineering and the State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China

b Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, WY, USA

c Department of Animal Science, University of Wyoming, Laramie, WY, USA

Abstract

Cationic polymer polyethyleneimine (PEI) can carry DNA across the cell membrane and enter the nucleus, and thus can be a very useful carrier for nuclear drug delivery; however, its highly positive charges make it toxic and not applicable for systemic drug delivery. Here, well-defined linear PEI (Mn = 1000 or 1500 or 2000)-block-polycaprolactone (Mn = 2000) (LPEI–PCL) was synthesized and used to fabricate a pH-triggered charge-reversal nanoparticle to solve this problem. LPEI's secondary amines are amidized as acid-labile β-carboxylic amides (LPEI/amide–PCL). LPEI/amide–PCL formed negatively charged nanoparticles with very low toxicity and low interaction with cells. Once in an acidic environment, the amides hydrolyze to regenerate the amine groups, producing LPEI–PCL nanoparticles carrying cationic charges. The LPEI–PCL escapes from the lysosomes and traverses into the nucleus. Folic-acid targeting groups are introduced to render the nanoparticles cancer-cell targeting capability. The nanoparticles efficiently enter folate-receptor overexpressing cancer cells and traverse to their nuclei. The DOX loaded in the carrier shows much improved cytotoxicity to cancer cells.

Graphical abstract: Linear polyethyleneimine-based charge-reversal nanoparticles for nuclear-targeted drug delivery

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Article information

DOI
https://doi.org/10.1039/C1JM13576G
Article type
Paper
Submitted
27 Jul 2011
Accepted
23 Sep 2011
First published
26 Oct 2011

J. Mater. Chem., 2011,21, 19114-19123

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Linear polyethyleneimine-based charge-reversal nanoparticles for nuclear-targeted drug delivery

Z. Zhou, Y. Shen, J. Tang, E. Jin, X. Ma, Q. Sun, B. Zhang, E. A. Van Kirk and W. J. Murdoch, J. Mater. Chem., 2011, 21, 19114 DOI: 10.1039/C1JM13576G

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