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Tytuł:
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Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo.
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Autorzy:
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Ewe A; Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany.
Panchal O; Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany.
Pinnapireddy SR; Department of Pharmaceutical Technology and Biopharmaceutics, Philipps-University Marburg, Germany.
Bakowsky U; Department of Pharmaceutical Technology and Biopharmaceutics, Philipps-University Marburg, Germany.
Przybylski S; Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
Temme A; Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany.
Aigner A; Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany. Electronic address: .
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Źródło:
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Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2017 Jan; Vol. 13 (1), pp. 209-218. Date of Electronic Publication: 2016 Aug 20.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: New York, NY : Elsevier, c2005-
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MeSH Terms:
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RNA Interference*
Liposomes/*chemistry
Polyethyleneimine/*chemistry
RNA, Small Interfering/*administration & dosage
Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Mice, Nude ; Prostatic Neoplasms/therapy ; RNA, Small Interfering/therapeutic use ; Tissue Distribution ; Xenograft Model Antitumor Assays
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Contributed Indexing:
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Keywords: Lipopolyplex; Liposome; Polyethlyenimine; RNAi; Survivin; siRNA delivery; siRNA therapy
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Substance Nomenclature:
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0 (Liposomes)
0 (RNA, Small Interfering)
9002-98-6 (Polyethyleneimine)
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Entry Date(s):
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Date Created: 20160825 Date Completed: 20171005 Latest Revision: 20181202
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Update Code:
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20240104
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DOI:
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10.1016/j.nano.2016.08.005
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PMID:
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27553077
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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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
