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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane
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Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane

机译：聚阳离子-siRNA纳米颗粒可在肾小球基底膜上分解

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摘要

Despite being engineered to avoid renal clearance, many cationic polymer (polycation)-based siRNA nanoparticles that are used for systemic delivery are rapidly eliminated from the circulation. Here, we show that a component of the renal filtration barrier-the glomerular basement membrane (GBM)-can disassemble cationic cyclodextrin-containing polymer (CDP)-based siRNA nanoparticles and, thereby, facilitate their rapid elimination from circulation. Using confocal and electron microscopies, positron emission tomography, and compartment modeling, we demonstrate that siRNA nanoparticles, but not free siRNA, accumulate and disassemble in the GBM. We also confirm that the siRNA nanoparticles do not disassemble in blood plasma in vitro and in vivo. This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between cationic delivery components and anionic nucleic acids (or other therapeutic entities).
机译：尽管经过工程设计可以避免肾脏清除，但许多用于全身性递送的基于阳离子聚合物（聚阳离子）的siRNA纳米颗粒却迅速从循环中消除。在这里，我们显示肾脏滤过屏障的组成部分-肾小球基底膜（GBM）-可以分解含阳离子环糊精的聚合物（CDP）基siRNA纳米颗粒，从而促进其从循环中的快速清除。使用共焦和电子显微镜检查，正电子发射断层扫描和隔室模型，我们证明了siRNA纳米颗粒（而非游离siRNA）在GBM中积累和拆卸。我们还证实，siRNA纳米粒子在体外和体内不会在血浆中分解。这种清除机制可能会影响主要通过阳离子传递成分和阴离子核酸（或其他治疗实体）之间的静电相互作用组装的任何纳米颗粒。

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