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首页> 美国政府科技报告 >Controlling the Diameter, Monodispersity, and Solubilityof Apoa1 Nanolipoprotein Particles Using Telodendrimer Chemistry.
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Controlling the Diameter, Monodispersity, and Solubilityof Apoa1 Nanolipoprotein Particles Using Telodendrimer Chemistry.

机译：用末端树枝状聚合物化学法控制apoa1纳米脂蛋白颗粒的直径，单分散性和溶解度。

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Nanolipoprotein particles (NLPs) are nanometer-scale discoidal particles that feature a phospholipid bilayer confined within an apolipoprotein “scaffold”, which are useful for solubilizing hydrophobic molecules such as drugs and membrane proteins. NLPs are synthesized either by mixing the purified apolipoprotein with phospholipids and other cofactors or by cell-free protein synthesis followed by self-assembly of the nanoparticles in the reaction mixture. Either method can be problematic regarding the production of homogeneous and monodispersed populations of NLPs, which also currently requires multiple synthesis and purification steps. Telodendrimers (TD) are branched polymers made up of a dendritic oligo-lysine core that is conjugated to linear polyethylene glycol (PEG) on one end, and the lysine “branches” are terminated with cholic acid (CA) moieties that enable the formation of nano-micelles in aqueous solution. We report herein that the addition of TD during cell-free synthesis of NLPs produces unique hybrid nanoparticles that have drastically reduced polydispersity compared to NLPs made in the absence of TD. This finding was supported by dynamic light scattering (DLS), fluorescence correlation spectroscopy (FCS), and cryo transmission electron microscopy (Cryo-EM). These techniques demonstrate the ability of TDs to modulate both the NLP size (6 to 30 nm) and polydispersity. The telodendrimer NLPs (TD-NLPs) also showed 80% less aggregation compared to NLPs alone. Furthermore, the versatility of these novel nanoparticles was shown through direct conjugation of small molecules such as fluorescent dyes directly to the TD as well as the insertion of a functional membrane protein.

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