Home > Papers

 
 
Linear PEI-based Charge-reversal Drug Conjugate for Targeted Cancer Cell Nuclear Drug Delivery
ZHOU Zhuxian 1,TANG Jianbin 2,SHEN Youqing 2 *
1.Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie 82071, USA
2.Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
*Correspondence author
#Submitted by
Subject:
Funding: The National Natural Science Foundation Key Program(No.21090352, 51390481), The National Basic Research Program(No.2014CB931900), The Doctoral Fund of Ministry of Education of China(No.20110101130007)
Opened online:26 December 2014
Accepted by: none
Citation: ZHOU Zhuxian,TANG Jianbin,SHEN Youqing.Linear PEI-based Charge-reversal Drug Conjugate for Targeted Cancer Cell Nuclear Drug Delivery[OL]. [26 December 2014] http://en.paper.edu.cn/en_releasepaper/content/4624499
 
 
Many cancer chemotherapy drugs target nuclear DNA to cause DNA damage and/or topoisomerase inhibition to induce cell death (apoptosis). Endocytosis is the primary route to delivery these drugs, which results in their accumulation in the endosomal-lysosomal trafficking pathway and loss of therapeutic activity. Thus, delivering such drugs directly to the nucleus would avoid the lysosomal accumulation and increase the drug efficiency. The cationic polymer linear PEI is capable of nuclear localization by 'Proton-Sponge Effect' (PSE), but its positive charge make it toxic and cannot be used in vivo. In this article, linear PEI is used to demonstrate a pH triggered charge-reversal carrier to solve this problem. The imines are amidized by masking of a lysosomal-pH-active agent. At neutral pH, the imine groups in the LPEI are covalently amidized with anhydride, thereby the polymer was masked by negative charge and inhibited of the membrane disruption activity. Under, acidic conditions such as those present within endosomes or lysosomes, the amide bond of them is cleaved, thus unmasking LPEI. The positively charged LPEI can then disrupt the endosomal membrane by PSE and resulting in delivery the drug into the cytoplasm and nuclei.
Keywords:anti-cancer drug delivery; charge-reversal; linear polyethylenimine; camptothecin
 
 
 

For this paper

  • PDF (0B)
  • ● Revision 0      
  • ● Print this paper
  • ● Recommend this paper to a friend
  • ● Add to my favorite list

    Saved Papers

    Please enter a name for this paper to be shown in your personalized Saved Papers list

Tags

Add yours

Related Papers

Statistics

PDF Downloaded 157
Bookmarked 0
Recommend 5
Comments Array
Submit your papers