884607-98-1Relevant articles and documents
One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA
Atochina-Vasserman, Elena N.,Billingsley, Margaret M.,Huang, Ning,Kim, Kyunghee,Liu, Matthew,Maurya, Devendra S.,Mitchell, Michael J.,Ni, Houping,Ona, Nathan,Percec, Virgil,Pochan, Darrin J.,Shahnawaz, Hamna,Weissman, Drew,Xiao, Qi,Zhang, Dapeng
supporting information, p. 12315 - 12327 (2021/08/20)
Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.
Structural transition of lipopolysaccharide and reduction in the biological activity by amphiphilic lipid with cationic amino acid
Li, Wenjing,Mochizuki, Shinichi,Sakurai, Kazuo
, p. 651 - 656 (2013/07/27)
Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, is a strong elicitor in the immune system by interacting with lipopolysaccharide- binding protein and CD14 with high specificity. The removal of LPS contamination in protein drug products expressed by bacteria is essential in pharmaceutical products for human use. Although polymyxin B (PMB)-immobilized columns are mainly used for removal of LPS, there are some problems, such as high production cost, and the toxicity of ligands. We synthesized aromatic lipids bearing lysine or arginine at the headgroup. These lipids form a complex with LPS through electrostatic interaction between cationic amino acids and phosphate groups in the lipid A backbone. The resultant complexes induce the structural transition of LPS from a cylindrical structure to a vesicle. Addition of amino-lipid/LPS complexes to RAW264.7 cells, a macrophage-like cell line, decrease the LPS activity. The efficiencies are higher than commonly used cationic compounds, such as dioleoyltrimethylammoniumpropane (DOTAP) and PMB. These results show that amphiphilic lipids with cationic amino acids can be used for deactivation of LPS.
Unique photoluminescence of diacetylene containing dendrimer self-assemblies: Application in positive and negative luminescence patterning
Kim, Joo-Ho,Lee, Eunyoung,Jeong, Young-Hwan,Jang, Woo-Dong
, p. 2356 - 2363 (2012/08/29)
A series of poly(benzyl ether) dendrimers with two benzene-1,3,5- tricarboxamide (BTA) units bridged by diacetylene were synthesized. The formation of hydrogen bonds between BTA units to form the supramolecular self-assembly was confirmed by FT-IR and AFM
Perylene bisimide dimer aggregates: Fundamental insights into self-assembly by NMR and UV/vis spectroscopy
Shao, Changzhun,Grüne, Matthias,Stolte, Matthias,Würthner, Frank
, p. 13665 - 13677 (2013/01/15)
A novel perylene bisimide (PBI) dye bearing one solubilizing dialkoxybenzyl and one bulky 2,5-di-tert-butylphenyl substituent was synthesized and its aggregation behavior was analyzed by NMR and UV/Vis spectroscopy in various chloroform/methylcyclohexane
