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  4. Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo
 
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2017
Journal Article
Title

Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo

Abstract
Therapeutic applications of RNA interference (RNAi) require efficient siRNA delivery strategies in vivo. Combining lipid-based carriers with polymeric nanoparticles offers the favorable properties of both systems. This is the first study to explore polyethylenimine-based lipopolyplexes comprising a low-molecular weight PEI and the phospholipid DPPC for therapeutic siRNA use. Lipopolyplex structures are analyzed by electron microscopy. Biological efficacies are demonstrated in vitro by cellular uptake, knockdown of the target oncogene survivin, and concomitant cell growth inhibition. Upon systemic administration in tumor-bearing mice, here performed by intraperitoneal (i.p.) injection, radioactive biodistribution assays show lipopolyplex-mediated delivery of intact siRNAs. Absence of blood serum parameter alterations, erythrocyte aggregation or immunostimulation, and the observation of animal well-being and stable body weight confirm biocompatibility. Exploring therapeutic efficacies in a preclinical model, a considerable inhibition of prostate carcinoma xenograft growth is achieved, paralleled by an ~65% survivin knockdown in the tumors. We, thus, demonstrate that PEI-based lipopolyplexes represent an efficient platform for therapeutic use of small RNAs
Author(s)
Ewe, Alexander
Universität Leipzig
Panchal, Omkar
Universität Leipzig
Pinnapireddy, Shashank Reddy
Universität Marburg
Bakowsky, Udo
Universität Marburg
Przybylski, Susanne
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
Temme, Achim
TU Dresden
Aigner, Achim
Universität Leipzig
Journal
Nanomedicine. Nanotechnology, biology and medicine  
DOI
10.1016/j.nano.2016.08.005
Language
English
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
Keyword(s)
  • lipopolyplex

  • Polyethylenimine

  • liposome

  • siRNA therapy

  • RNAi

  • therapeutic siRNA delivery

  • survivin

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