| Synthesis, characterization, and gene delivery of poly-L-lysine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular architectures. | |
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MedLine Citation:
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PMID: 17705440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Macromolecules with defined nanosizes--nanoglobules--were synthesized and characterized as novel drug carriers with precise molecular architectures. Poly-L-lysine dendrimers with a cubic octa(3-aminopropyl)silsesquioxane (OAS) core, (L-lysine 8-OAS, (L-lysine) 16-(L-lysine) 8-OAS, (L-lysine) 32-(L-lysine) 16-(L-lysine) 8-OAS, and (L-lysine) 64-(L-lysine) 32-(L-lysine) 16-(L-lysine) 8-OAS, were divergently synthesized by solution phase peptide chemistry in good yield and purity. Matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectrometry showed complete substitution of the surface amino groups of lower generation dendrimers during synthesis, as well as precisely defined molecular architectures of the nanoglobules. The structures of the nanoglobules were further characterized by (1)H- and (13)C-NMR and 2D-NMR (correlation spectroscopy (COSY) and pulsed-field-gradient heteronuclear multiple quantum correlation (gHMQC)) spectroscopy. The (1)H-NMR spectroscopy revealed that the nanoglobules had a relatively rigid molecular architecture. Cytotoxicity studies showed that these nanoglobules exhibited a size-dependent toxicity, but it was much lower than that of linear poly-L-lysine. Preliminary in vitro nucleic acid delivery studies have shown that these globular dendrimers can efficiently deliver plasmid DNA to MDA-MB-231 cells. These nanoglobules hold much promise as safe drug carriers with precisely defined molecular architecture. |
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Authors:
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Todd L Kaneshiro; Xuli Wang; Zheng-Rong Lu |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-08-17 |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 4 ISSN: 1543-8384 ISO Abbreviation: Mol. Pharm. Publication Date: 2007 Sep-Oct |
Date Detail:
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Created Date: 2007-10-02 Completed Date: 2007-12-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 759-68 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Survival / drug effects Dendrimers / chemical synthesis*, chemistry, toxicity Drug Carriers / chemistry* Gene Transfer Techniques Humans Magnetic Resonance Spectroscopy Molecular Structure Nanoparticles / chemistry* Organosilicon Compounds / chemical synthesis*, chemistry, toxicity Polylysine / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA 097465/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dendrimers; 0/Drug Carriers; 0/Organosilicon Compounds; 25104-18-1/Polylysine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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