863591-45-1Relevant academic research and scientific papers
Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers
Zhang, Dapeng,Atochina-Vasserman, Elena N.,Maurya, Devendra S.,Liu, Matthew,Xiao, Qi,Lu, Juncheng,Lauri, George,Ona, Nathan,Reagan, Erin K.,Ni, Houping,Weissman, Drew,Percec, Virgil
supporting information, p. 17975 - 17982 (2021/11/10)
Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.
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.
Synthesis and nonlinear optical properties of branched pyrroline chromophores
Liu, Jialei,Hou, Wenjun,Feng, Shuwen,Qiu, Ling,Liu, Xinhou,Zhen, Zhen
experimental part, p. 439 - 444 (2012/01/03)
New tricyanopyrroline (TCP) chromophores with rigid-flexible dendron were prepared for second-order nonlinear optical (NLO) application. The chromophores were fully characterized using ultraviolet-visible spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. Thermal gravimetric analysis (TGA) revealed that the chromophores had excellent thermal stability. Large λmax and high solvate chromic effects revealed that the chromophores had large second-order optical nonlinearity. The electro-optic coefficients (r33) were measured in the chromophores-doped poly(bisphenol A carbonate) films at the fundamental wavelength of 1310 nm, and the highest γ33 achieved was 217 pmV-1. Copyright
The synthesis of symmetric and asymmetric perylene derivatives and their optical properties
Oh, Sang Hyun,Kim, Bong Gun,Yun, Sun Ju,Maheswara, Muchchintala,Kim, Ketack,Do, Jung Yun
experimental part, p. 37 - 42 (2010/10/21)
Symmetric bisimidazole and asymmetric imide-imidazole derivatives having a perylene structure were synthesized. Long, hyperbranched alkyl groups, attached to the benzimidazole moeity, enhanced the solubility of the imidazole derivatives. Soluble asymmetric imide-imidazoles were prepared using 1,2-diaminophenyls which contained methoxy, nitro and ester groups. The effects of both electron-withdrawing and donating groups were examined optically and electronically using both absorption and emission spectroscopy. Photoluminescence spectroscopy revealed that the various perylene derivatives displayed varying quantum yield; frontier orbital energy levels were determined using cyclic voltammetric analysis. The asymmetric imide-imidazole displayed the transient, electronic and optical properties of symmetric bisimide and symmetric bisimidazole perylene derivatives. Nitro derivation reduced the LUMO energy level of the asymmetric perylene by 0.05?eV while methoxy derivation increased it by 0.07?eV, in comparison with that of the unsubstituted, asymmetric perylene. Either bathochromic or hypsochromic spectral shifts of the asymmetric imidazoles were observed in solid film, depending on electronic substituent.
A new approach toward light-harvesting reverse micelles from donor-acceptor miscible blends
Takahashi, Masaki,Nishizawa, Natsuko,Ohno, Shuhei,Kakita, Masahiro,Fujita, Norifumi,Yamashita, Mitsuji,Sengoku, Tetsuya,Yoda, Hidemi
experimental part, p. 2669 - 2677 (2009/06/20)
In the present paper, we report a new approach toward light-harvesting reverse micellar systems from molecular blends of anthracene and perylene building blocks. The self-assembly initiated by protonation of the molecular blends gave rise to the mixed rev
