| Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for cancer cell targeting. | |
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MedLine Citation:
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PMID: 22142685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cancer-targeting drug delivery can be based on the rational design of a therapeutic platform. This approach is typically achieved by the functionalization of a nanoparticle with two distinct types of molecules, a targeting ligand specific for a cancer cell, and a cytotoxic molecule to kill the cell. The present study aims to evaluate the validity of an alternative simplified approach in the design of cancer-targeting nanotherapeutics: conjugating a single type of molecule with dual activities to nanoparticles, instead of coupling a pair of orthogonal molecules. Herein we investigate whether this strategy can be validated by its application to methotrexate, a dual-acting small molecule that shows cytotoxicity because of its potent inhibitory activity against dihydrofolate reductase and that binds folic acid receptor, a tumor biomarker frequently upregulated on the cancer cell surface. This article describes a series of dendrimer conjugates derived from a generation 5 polyamidoamine (G5 PAMAM) presenting a multivalent array of methotrexate and also demonstrates their dual biological activities by surface plasmon resonance spectroscopy, a cell-free enzyme assay, and cell-based experiments with KB cancer cells. |
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Authors:
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Ming-Hsin Li; Seok Ki Choi; Thommey P Thomas; Ankur Desai; Kyung-Hoon Lee; Alina Kotlyar; Mark M Banaszak Holl; James R Baker |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-11-23 |
Journal Detail:
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Title: European journal of medicinal chemistry Volume: 47 ISSN: 1768-3254 ISO Abbreviation: Eur J Med Chem Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-16 Completed Date: 2012-05-29 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 0420510 Medline TA: Eur J Med Chem Country: France |
Other Details:
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Languages: eng Pagination: 560-72 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
Affiliation:
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Michigan Nanotechnology Institute for Medicine and Biological Sciences, and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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chemistry,
pharmacology Dendrimers / chemistry* Folic Acid Antagonists / chemistry, pharmacology Humans KB Cells Methotrexate / chemistry*, pharmacology* Molecular Conformation Molecular Dynamics Simulation Nanoconjugates / chemistry* Surface Plasmon Resonance Tetrahydrofolate Dehydrogenase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1 R01 CA119409/CA/NCI NIH HHS; R01 CA119409-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Dendrimers; 0/Folic Acid Antagonists; 0/Nanoconjugates; 0/PAMAM Starburst; 59-05-2/Methotrexate; EC 1.5.1.3/Tetrahydrofolate Dehydrogenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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