Cationic Solid Lipid Nanoparticles Reconstituted from Low Density Lipoprotein Components for Delivery of siRNA

2008 ◽  
Vol 5 (4) ◽  
pp. 622-631 ◽  
Author(s):  
Hyun Ryoung Kim ◽  
In Kyoung Kim ◽  
Ki Hyun Bae ◽  
Soo Hyeon Lee ◽  
Yuhan Lee ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
Low Density ◽  
Solid Lipid

scholarly journals Tumor-Targeted Delivery of Paclitaxel Using Low Density Lipoprotein-Mimetic Solid Lipid Nanoparticles

2015 ◽  
Vol 12 (4) ◽  
pp. 1230-1241 ◽  
Author(s):  
Jin-Ho Kim ◽  
Youngwook Kim ◽  
Ki Hyun Bae ◽  
Tae Gwan Park ◽  
Jung Hee Lee ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Solid Lipid Nanoparticles ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
Low Density ◽  
Solid Lipid

scholarly journals Lipid nanoparticles incorporating a GalNAc ligand enable in vivo liver ANGPTL3 editing in wild-type and somatic LDLR knockout non-human primates

2021 ◽  
Author(s):  
Lisa N Kasiewicz ◽  
Souvik Biswas ◽  
Aaron Beach ◽  
Huilan Ren ◽  
Chaitali Dutta ◽  
...  
Keyword(s):  
Gene Editing ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Wild Type ◽  
Guide Rna ◽  
Delivery Technology

Standard lipid nanoparticles (LNPs) deliver gene editing cargoes to hepatocytes through receptor-mediated uptake via the low-density lipoprotein receptor (LDLR). Homozygous familial hypercholesterolemia (HoFH) is a morbid genetic disease characterized by complete or near-complete LDLR deficiency, markedly elevated blood low-density lipoprotein cholesterol (LDL-C) levels, and premature atherosclerotic cardiovascular disease. In order to enable in vivo liver gene editing in HoFH patients, we developed a novel LNP delivery technology that incorporates a targeting ligand - N-acetylgalactosamine (GalNAc) - which binds to the asialoglycoprotein receptor (ASGPR). In a cynomolgus monkey (Macaca fascicularis) non-human primate (NHP) model of HoFH created by somatic knockout of the LDLR gene via CRISPR-Cas9, treatment with GalNAc-LNPs formulated with an adenine base editor mRNA and a guide RNA (gRNA) targeting the ANGPTL3 gene yielded ~60% whole-liver editing and ~94% reduction of blood ANGPTL3 protein levels, whereas standard LNPs yielded minimal editing. Moreover, in wild-type NHPs, the editing achieved by GalNAc-LNPs compared favorably to that achieved by standard LNPs, suggesting that GalNAc-LNP delivery technology may prove useful across a range of in vivo therapeutic applications targeting the liver.

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

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