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The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors
Title: | The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors |
Authors: | Hatakeyama, Hiroto Browse this author →KAKEN DB | Akita, Hidetaka Browse this author →KAKEN DB | Harashima, Hideyoshi Browse this author →KAKEN DB |
Keywords: | liposome | small interfering RNA | tumor | multifunctional envelope-type nano device | drug delivery system |
Issue Date: | Jun-2013 |
Publisher: | Pharmaceutical Soc Japan |
Journal Title: | Biological & Pharmaceutical Bulletin |
Volume: | 36 |
Issue: | 6 |
Start Page: | 892 |
End Page: | 899 |
Publisher DOI: | 10.1248/bpb.b13-00059 |
PMID: | 23727912 |
Abstract: | Gene and nucleic acid therapy is expected to play a major role in the next generation of agents for cancer treatment. We have recently developed a multifunctional envelope-type nano device (MEND) for use as a novel nonviral gene delivery system. The modification of polyethyleneglycol (PEG), i.e., PEGylation, is a useful method for achieving a longer circulation time for the delivery of MEND to a tumor via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity of the delivery system. For successful nucleic acid delivery for cancer treatment, the crucial problem associated with the use of PEG, i.e., the "PEG dilemma" must be resolved. In this review, we describe the development and applications of MEND and discuss various strategies for overcoming the PEG dilemma based on the manipulation of both pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release. To increase cellular uptake, target ligands including proteins, peptides, antibodies and aptamers that recognize molecules specifically expressed on tumors are first introduced. Second, cleavable PEG systems are described. The cleavage of PEG from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. Then, endosomal fusogenic peptides are discussed. Finally, pH-sensitive liposomes using pH-sensitive lipids are described. |
Type: | article |
URI: | http://hdl.handle.net/2115/53045 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 浩人
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