Document Detail


Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo.
MedLine Citation:
PMID:  22286008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, stearyl triphenylphosphonium (STPP)-modified liposomes (STPP-L) were reported to target mitochondria. To overcome a non-specific cytotoxicity of STPP-L, we synthesized a novel polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate with the TPP group attached to the distal end of the PEG block (TPP-PEG-PE). This conjugate was incorporated into the liposomal lipid bilayer, and the modified liposomes were studied for their toxicity, mitochondrial targeting, and efficacy in delivering paclitaxel (PTX) to cancer cells in vitro and in vivo. These TPP-PEG-PE-modified liposomes (TPP-PEG-L), surface grafted with as high as 8 mol% of the conjugate, were less cytotoxic compared to STPP-L or PEGylated STPP-L. At the same time, TPP-PEG-L demonstrated efficient mitochondrial targeting in cancer cells as shown by confocal microscopy in co-localization experiments with stained mitochondria. PTX-loaded TPP-PEG-L demonstrated enhanced PTX-induced cytotoxicity and anti-tumor efficacy in cell culture and mouse experiments compared to PTX-loaded unmodified plain liposomes (PL). Thus, TPP-PEG-PE can serve as a targeting ligand to prepare non-toxic liposomes as mitochondria-targeted drug delivery systems (DDS).
Authors:
Swati Biswas; Namita S Dodwadkar; Pranali P Deshpande; Vladimir P Torchilin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-20
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  159     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-08     Completed Date:  2012-09-28     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  393-402     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Center for Pharmaceutical Biotechnology and Nanomedicine, 360 Huntington Avenue, 312 Mugar Hall, Northeastern University, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / administration & dosage*,  pharmacokinetics,  therapeutic use,  toxicity
Cell Survival / drug effects
Drug Carriers / chemistry*,  pharmacology,  toxicity
Drug Compounding
Endocytosis / drug effects
Female
Flow Cytometry
HeLa Cells
Humans
Lipid Bilayers
Liposomes
Mammary Neoplasms, Experimental / drug therapy,  metabolism,  pathology
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Mitochondria / drug effects*
Molecular Structure
Neoplasm Transplantation
Paclitaxel / administration & dosage*,  pharmacokinetics,  therapeutic use,  toxicity
Particle Size
Phosphatidylethanolamines / chemistry*,  pharmacology,  toxicity
Polyethylene Glycols / chemistry*,  pharmacology,  toxicity
Surface Properties
Grant Support
ID/Acronym/Agency:
R01 CA 128486/CA/NCI NIH HHS; R01 CA121838/CA/NCI NIH HHS; R01 CA121838/CA/NCI NIH HHS; R01 CA121838-05/CA/NCI NIH HHS; R01 CA128486/CA/NCI NIH HHS; R01 CA128486-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Drug Carriers; 0/Lipid Bilayers; 0/Liposomes; 0/Phosphatidylethanolamines; 0/Polyethylene Glycols; 33069-62-4/Paclitaxel
Comments/Corrections

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