Modeling the proton sponge hypothesis: examining proton sponge effectiveness for enhancing intracellular gene delivery through multiscale modeling.
Modeling the proton sponge hypothesis: examining proton sponge effectiveness for enhancing intracellular gene delivery through multiscale modeling.
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DOI：
10.1080/09205063.2012.690282
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Meng WS
中科院分区：
文献类型：
--
作者：
Freeman EC;Weiland LM;Meng WS
树枝状聚合物已被提议作为治疗性基因递送平台。它们的上级转染效率归因于它们缓冲内体酸化并附着于核酸的能力。为了有效转染，策略是合成优化这两种特性的新型树枝状聚合物，但内体中缓冲行为的预测仍然难以捉摸。有人建议，缓冲树枝状聚合物诱导的渗透压足以破裂的内体和释放核酸，形成螯合最内化的外源性物质。这里介绍的是一项计算研究的结果，该研究模拟了质子驱动的内体爆发或“质子海绵效应”。该方法建立在以前的细胞模拟的努力，通过连接以前的模型与海绵质子化模型，然后观察内体肿胀和酸化的影响。使用报告的实验数据进行校准和验证，模拟提供了对定义合适的树枝状聚合物的特性的见解，用于增强作为聚合物结构的函数的基因递送。
Dendrimers have been proposed as therapeutic gene delivery platforms. Their superior transfection efficiency is attributed to their ability to buffer the acidification of the endosome and attach to the nucleic acids. For effective transfection the strategy is to synthesize novel dendrimers that optimize both of these traits, but the prediction of the buffering behavior in the endosome remains elusive. It is suggested that buffering dendrimers induce an osmotic pressure sufficient to rupture the endosome and release nucleic acids, which forms to sequestrate most internalized exogenous materials. Presented here are the results of a computational study modeling osmotically-driven endosome burst, or the “proton sponge effect.” The approach builds on previous cellular simulation efforts by linking the previous model with a sponge protonation model then observing the impact on endosomal swelling and acidification. Calibrated and validated using reported experimental data, the simulations offer insights into defining the properties of suitable dendrimers for enhancing gene delivery as a function of polymer structure.
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影响因子：
--
作者：
LENCER, WI;WEYER, P;BROWN, D
通讯作者：
BROWN, D
影响因子：
5.6
作者：
PRICE, HD;THOMPSON, TE
通讯作者：
THOMPSON, TE
DOI：
10.1177/1045389x08092276
发表时间：
2009-01-01
影响因子：
2.7
作者：
Freeman, Eric;Weiland, Lisa Mauck
通讯作者：
Weiland, Lisa Mauck
影响因子：
6.2
作者：
Funhoff, AM;van Nostrum, CF;Hennink, WE
通讯作者：
Hennink, WE
影响因子：
4.6
作者：
Koper, Ger J. M.;Borkovec, Michal
通讯作者：
Borkovec, Michal