Source:http://linkedlifedata.com/resource/pubmed/id/18294280
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2008-4-2
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pubmed:abstractText |
Causing damage to angiogenic vessels is a promising approach for cancer chemotherapy. The present study is a codification of a designed liposomal drug delivery system (DDS) for antineovascular therapy (ANET) with 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC). The authors have previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl CNDAC (DPP-CNDAC), a phospholipid derivative of the novel antitumor nucleoside CNDAC, is quite useful for ANET. DPP-CNDAC liposomes modified with APRPG, a peptide having affinity toward angiogenic vessels, efficiently suppressed tumor growth by damaging angiogenic endothelial cells. In the present study, the authors masked the hydrophilic moiety of DPP-CNDAC, namely, CNDAC, on the liposomal surface with APRPG-polyethyleneglycol (PEG) conjugate to improve the availability of DPP-CNDAC liposomes. The use of the APRPG-PEG conjugate attenuated the negative zeta-potential of the DPP-CNDAC liposomes and reduced the agglutinability of them in the presence of serum. These effects improved the blood level of DPP-CNDAC liposomes in colon 26 NL-17 tumor-bearing BALB/c male mice, resulting in enhanced accumulation of them in the tumor. Laser scanning microscopic observations indicated that APRPG-PEG-modified DPP-CNDAC liposomes (LipCNDAC/APRPG-PEG) colocalized with angiogenic vessels and strongly induced apoptosis of tumor cells, whereas PEG-modified DPP-CNDAC liposomes (LipCNDAC/PEG) did not. In fact, LipCNDAC/APRPG-PEG suppressed the tumor growth more strongly compared to LipCNDAC/PEG and increased significantly the life span of the mice. The present study is a good example of an effective liposomal DDS for ANET that is characterized by: (i) phospholipid derivatization of a certain anticancer drug to suit the liposomal formulation; (ii) PEG-shielding for masking undesirable properties of the drug on the liposomal surface; and (iii) active targeting to angiogenic endothelial cells using a specific probe.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Arabinonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethylene Glycols,
http://linkedlifedata.com/resource/pubmed/chemical/dpp-cndac
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1349-7006
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1029-33
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pubmed:meshHeading |
pubmed-meshheading:18294280-Animals,
pubmed-meshheading:18294280-Antineoplastic Agents,
pubmed-meshheading:18294280-Arabinonucleotides,
pubmed-meshheading:18294280-Drug Delivery Systems,
pubmed-meshheading:18294280-Liposomes,
pubmed-meshheading:18294280-Male,
pubmed-meshheading:18294280-Mice,
pubmed-meshheading:18294280-Mice, Inbred BALB C,
pubmed-meshheading:18294280-Neoplasms, Experimental,
pubmed-meshheading:18294280-Neovascularization, Pathologic,
pubmed-meshheading:18294280-Polyethylene Glycols,
pubmed-meshheading:18294280-Tissue Distribution,
pubmed-meshheading:18294280-Tumor Cells, Cultured
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pubmed:year |
2008
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pubmed:articleTitle |
Antineovascular therapy with angiogenic vessel-targeted polyethyleneglycol-shielded liposomal DPP-CNDAC.
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pubmed:affiliation |
Department of Medical Biochemistry and Global COE, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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