91925-82-5Relevant 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.
Sequence-defined dendrons dictate supramolecular cogwheel assembly of dendronized perylene bisimides
Partridge, Benjamin E.,Wang, Li,Sahoo, Dipankar,Olsen, James T.,Leowanawat, Pawaret,Roche, Cecilé,Ferreira, Henrique,Reilly, Kevin J.,Zeng, Xiangbing,Ungar, Goran,Heiney, Paul A.,Graf, Robert,Spiess, Hans W.,Percec, Virgil
supporting information, p. 15761 - 15766 (2019/10/11)
A dendronized perylene bisimide (PBI) that self-organizes into hexagonal arrays of supramolecular double helices with identical single crystal-like order that disregards chirality was recently reported. A cogwheel model of selfassembly that explains this process was proposed. Accessing the highly ordered cogwheel phase required very slow heating and cooling or extended periods of annealing. Analogous PBIs with linear alkyl chains did not exhibit the cogwheel assembly. Here a library of sequence-defined dendrons containing all possible compositions of linear and racemic alkyl chains was employed to construct self-assembling PBIs. Thermal and structural analysis of their assemblies by differential scanning calorimetry (DSC) and fiber X-ray diffraction (XRD) revealed that the incorporation of n-alkyl chains accelerates the formation of the high order cogwheel phase, rendering the previously invisible phase accessible under standard heating and cooling rates. Small changes to the primary structure, as constitutional isomerism, result in significant changes to macroscopic properties such as melting of the periodic array. This study demonstrated how changes to the sequencedefined primary structure, including the relocation of methyl groups between two constitutional isomers, dictate tertiary and quaternary structure in hierarchical assemblies. This led to the discovery of a sequence that self-organizes the cogwheel assembly much faster than even the corresponding homochiral compounds and demonstrated that defined-sequence, which has long been recognized as determinant for the complex structure of biomacromolecules including proteins and nucleic acids plays the same role also in supramolecular synthetic systems.
DENDRONIZED METALLIC OXIDE NANOPARTICLES, A PROCESS FOR PREPARING THE SAME AND THEIR USES
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Page/Page column 89, (2015/11/30)
The present invention relates to dendronized metallic oxide nanoparticles, a process for preparing the same and their uses.
