Kim, Kyoung-Ran Kim, Junghyun Back, Ji Hyun Lee, Ji Eun Ahn, Dae-Ro 2024-01-19T12:01:57Z 2024-01-19T12:01:57Z 2022-07-14 2022-05 1936-0851 https://pubs.kist.re.kr/handle/201004/115180 The protein corona is a protein layer formed on the surface of nanoparticles administered in vivo and considerably affects the in vivo fate of nanoparticles. Although it is challenging to control protein adsorption on nanoparticles precisely, the protein corona may be harnessed to develop a targeted drug delivery system if the nanoparticles are decorated with a ligand with enhanced affinity to target tissue- and cell-homing proteins. Here, we prepared a DNA tetrahedron with trivalent cholesterol conjugation (Chol(3)-Td) that can induce enhanced interaction with lipoproteins in serum, which in situ generates the lipoprotein-associated protein corona on a DNA nanostructure favorable for cells abundantly expressing lipoprotein receptors in the liver, such as hepatocytes in healthy mice and myofibroblasts in fibrotic mice. Chol(3)-Td was further adopted for liver delivery of antisense oligonucleotide (ASO) targeting TGF-beta 1 mRNA to treat liver fibrosis in a mouse model. The potency of ASO@Chol(3)-Td was comparable to that of ASO conjugated with the clinically approved liver-targeting ligand, trivalent N-acetylgalactosamine (GalNAc3), demonstrating the potential of Chol(3)-Td as a targeted delivery system for oligonucleotide therapeutics. This study suggests that controlled seeding of the protein corona on nanomaterials can provide a way to steer nanoparticles into the target area. English American Chemical Society Cholesterol-Mediated Seeding of Protein Corona on DNA Nanostructures for Targeted Delivery of Oligonucleotide Therapeutics to Treat Liver Fibrosis Article 10.1021/acsnano.1c08508 1 ACS Nano, v.16, no.5, pp.7331 - 7343 ACS Nano 16 5 7331 7343 N scie scopus 000821333100001 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article; Early Access GROWTH-FACTOR-BETA CELLS MESENCHYMAL TRANSITION GENE SINUSOIDS ORIGAMI PATHWAY DESIGN protein corona targeted delivery liver delivery oligonucleotide therapeutics cholesterol conjugation DNA tetrahedron