Document Detail


Listeriolysin O enhances cytoplasmic delivery by Her-2 targeting liposomes.
MedLine Citation:
PMID:  20201742     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To enhance cytoplasmic delivery of liposomal contents to breast cancer cells, the authors have attached the pore-forming protein, listeriolysin O (LLO), to thermosensitive liposomes. The antibody trastuzumab (Herceptin) was also conjugated with the outer surface of the liposomes, resulting in highly specific binding and internalization into mammary epithelial cells that overexpress the human epidermal growth factor receptor 2 (Her-2). The liposomes were preloaded with a marker fluorescent dye, and the effect of LLO on the distribution of dye within the cells was monitored using fluorescence microscopy. Owing to the thermosensitive nature of the liposomes, hyperthermia at 42 degrees C triggered the release of the encapsulated fluorescent calcein from the endocytosed liposomes into the interior of the endosomes. LLO, when conjugated to these liposomes, subsequently formed pores in the endosomal membrane, allowing calcein to flow out of the endosomal compartment into the cytoplasm. Her-2-targeted liposomes bearing LLO delivered a 22-fold greater concentration of calcein to mammary epithelial cells that overexpress Her-2 compared to cells with normal Her-2 expression. Thus, the addition of LLO to preformed liposomes offers a method for significantly enhancing delivery of liposomal contents to the cytoplasm of targeted cells.
Authors:
Max Kullberg; Jesse Lee Owens; Kristine Mann
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of drug targeting     Volume:  18     ISSN:  1029-2330     ISO Abbreviation:  J Drug Target     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-08-10     Revised Date:  2011-04-18    
Medline Journal Info:
Nlm Unique ID:  9312476     Medline TA:  J Drug Target     Country:  England    
Other Details:
Languages:  eng     Pagination:  313-20     Citation Subset:  IM    
Affiliation:
Biomedical Program, University of Alaska, Anchorage, Alaska 99508, USA. afmpk@uaa.alaska.edu
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MeSH Terms
Descriptor/Qualifier:
Bacterial Toxins / administration & dosage*
Cell Line
Cytoplasm / metabolism*
Fluorescent Dyes
Heat-Shock Proteins / administration & dosage*
Hemolysin Proteins / administration & dosage*
Humans
Liposomes*
Microscopy, Fluorescence
Receptor, erbB-2 / drug effects*
Chemical
Reg. No./Substance:
0/Bacterial Toxins; 0/Fluorescent Dyes; 0/Heat-Shock Proteins; 0/Hemolysin Proteins; 0/Liposomes; 72270-41-8/hlyA protein, Listeria monocytogenes; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections
Comment In:
Nanomedicine (Lond). 2011 Feb;6(2):314

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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