2007
DOI: 10.1021/bc070126m
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Site-Specific Delivery of Oligonucleotides to Hepatocytes after Systemic Administration

Abstract: We previously complexed ODN with galactosylated poly (L-lysine) (Gal-PLL) to enhance its site specific delivery to hepatocytes. To avoid the use of polycations, in this study we conjugated galactosylated poly (ethylene glycol) (Gal-PEG (MW of PEG: 3486±500Da)) to ODN via an acid labile ester linkage of β-thiopropionate. Following tail vein injection into rats, Gal-PEG-33 P-ODN rapidly cleared from the circulation and 60.2% of the injected dose accumulated in the liver at 30 min post injection, which was signif… Show more

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Cited by 40 publications
(60 citation statements)
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“…However, work is still needed on the sensitivity of these drug carriers to the applied stimuli. Some major drawbacks in the field may include the off-tumortargeting caused by non-specific stimuli such as overexpression of target enzymes in non-cancer cells (Spallarossa et al, 2006;Cheng et al, 2009) inaccurate utilization of stimuli such as uncontrolled depth of magnetic field and heating (Sawant et al, 2006;Zhu et al, 2009;Deng et al, 2011) and slow response to applied stimulus (Zhu et al, 2008;Wong et al, 2011).…”
Section: Remained Challengesmentioning
confidence: 99%
“…However, work is still needed on the sensitivity of these drug carriers to the applied stimuli. Some major drawbacks in the field may include the off-tumortargeting caused by non-specific stimuli such as overexpression of target enzymes in non-cancer cells (Spallarossa et al, 2006;Cheng et al, 2009) inaccurate utilization of stimuli such as uncontrolled depth of magnetic field and heating (Sawant et al, 2006;Zhu et al, 2009;Deng et al, 2011) and slow response to applied stimulus (Zhu et al, 2008;Wong et al, 2011).…”
Section: Remained Challengesmentioning
confidence: 99%
“…Since oligonucleotides and siRNAs are readily modified by other functional molecules to improve their stability and pharmacokinetic behaviors (134), the conjugation reaction was widely used to link nucleic acid with functional lipids (135,136), polymers (134,137), and nanoparticles (138). ODN or siRNA can be covalently linked with functional molecules via non-degradable or degradable linkage, such as acid-labile ester (134,139) and reducible disulfide bond (140,141).…”
Section: Oligonucleotide and Sirna Conjugatesmentioning
confidence: 99%
“…Systemic administration of siRNA-cholesterol resulted in silencing of apoB mRNA in liver and jejunum as well as reduction of the total cholesterol level (136). Water soluble polymers with the functional terminal groups were alos used to conjugate with nucleic acids, such as PEG (134,141) and HPMA (137) (Figure 2.6B). We conjugated galactosylated poly (ethylene glycol) (Gal-PEG) to ODN via an acid-labile ester linkage of β-thiopropionate.…”
Section: Oligonucleotide and Sirna Conjugatesmentioning
confidence: 99%
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