Document Detail


Synthesis, characterization, and gene delivery of poly-L-lysine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular architectures.
MedLine Citation:
PMID:  17705440     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Todd L Kaneshiro; Xuli Wang; Zheng-Rong Lu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-08-17
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  4     ISSN:  1543-8384     ISO Abbreviation:  Mol. Pharm.     Publication Date:    2007 Sep-Oct
Date Detail:
Created Date:  2007-10-02     Completed Date:  2007-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  759-68     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R01 CA 097465/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Dendrimers; 0/Drug Carriers; 0/Organosilicon Compounds; 25104-18-1/Polylysine

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