| 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. | |
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MedLine Citation:
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PMID: 22286008 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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). |
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Authors:
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Swati Biswas; Namita S Dodwadkar; Pranali P Deshpande; Vladimir P Torchilin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-20 |
Journal Detail:
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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:
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Created Date: 2012-05-08 Completed Date: 2012-09-28 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: Netherlands |
Other Details:
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Languages: eng Pagination: 393-402 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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Center for Pharmaceutical Biotechnology and Nanomedicine, 360 Huntington Avenue, 312 Mugar Hall, Northeastern University, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Antineoplastic Agents, Phytogenic; 0/Drug Carriers; 0/Lipid Bilayers; 0/Liposomes; 0/Phosphatidylethanolamines; 0/Polyethylene Glycols; 33069-62-4/Paclitaxel |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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