Synthesis, characterization, and gene delivery of poly-L-lysine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular architectures.
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.
Kaneshiro
Todd L
TL
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
Wang
Xuli
X
Lu
Zheng-Rong
ZR
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011107:Polylysine / Q000737:chemistry*
D050091:Dendrimers; D004337:Drug Carriers; D017646:Organosilicon Compounds; D011107:Polylysine