Plasmid-templated shape control of condensed DNA-block copolymer nanoparticles.
Plasmid-templated shape control of condensed DNA-block copolymer nanoparticles.
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DOI：
10.1002/adma.201202932
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发表时间：
2013-01-11
影响因子：
29.4
通讯作者：
Mao, Hai-Quan
中科院分区：
文献类型：
--
作者：
Jiang, Xuan;Qu, Wei;Pan, Deng;Ren, Yong;Williford, John-Michael;Cui, Honggang;Luijten, Erik;Mao, Hai-Quan
尽管这些聚阳离子-DNA纳米颗粒中的许多在细胞培养中显示出相对高水平的转染效率，但它们在体内的表现令人失望。[2]这种低的体内递送效率部分是由于对纳米颗粒的物理性质和胶体稳定性的控制不足。已经开发了几种方法来提高DNA纳米颗粒在生理介质中的胶体稳定性，包括聚乙二醇（PEG）缀合、聚离子涂层和将DNA凝聚成胶束。[3]然而，到目前为止，还没有有效的方法来控制和调整含有质粒DNA的纳米颗粒在这个尺寸范围内的形状。考虑到最近的几项研究表明纳米颗粒形状在调节其细胞摄取和体内运输中的重要性，这种限制特别紧迫，[4 - 6]如巨噬细胞对金纳米颗粒的摄取所证明的，[7]对于血管中纳米颗粒的边缘动力学，[6]以及用于有机和无机纳米颗粒的组织分布和循环稳定性以及因此的药物递送效率。[5，8]我们注意到这些形状的纳米颗粒都没有用于包装和递送质粒DNA。在这里，我们报告了一种通过在DNA与PEG-b-聚磷酰胺酯（PPA）缩合期间改变溶剂极性来调节质粒DNA纳米颗粒的新方法[9，10]（图1）。将共聚物（图S1和表S1）和质粒DNA分别溶解在固定体积比的二甲基甲酰胺（DMF）-水混合物中，并以预定的共聚物与DNA比例混合两种溶液以实现有效的DNA缩合，[11]我们观察到形态的显着变化（图1b-e）。在纯水中形成的胶束呈现长蠕虫状和环状的混合形态（图1b）。在一个3：7（v/v）DMF-水混合物中，一小部分球形和棒状胶束出现在主要的蠕虫状结构中（图1c），其长度比在水中观察到的短。当DMF/水体积比增加到5：5时，超过90%的胶束采用均匀的棒状形态（图1d），直径为24 ± 3 nm，长度为70 ± 10 nm。此外，我们观察到一小部分直径为41 ± 7 nm的球形胶束。DMF/水体积比进一步增加至7：3导致形成直径为40 ± 5 nm的高度均匀的球形胶束（图1e）。使用低温TEM成像证实了这些结构（图S2）。这种产生不同形状的DNA致密胶束的方法并不局限于使用DMF作为共溶剂;我们已经使用二甲基亚砜（DMSO）-水溶剂混合物成功制备了一系列类似的胶束（图S3）。
Although many of these polycation–DNA nanoparticles display relatively high levels of transfection efficiency in cell culture, their performance in vivo has been disappointing.[2] This low in vivo delivery efficiency partly results from insufficient control over the physical properties and colloidal stability of the nanoparticles. Several methods have been developed to improve colloidal stability of DNA nanoparticles in physiological media, including polyethylene glycol (PEG)-conjugation, polyionic coating, and condensing DNA into polyelectrolyte micelles.[3] However, until now there has been no effective method to control and tune the shape of plasmid DNA-containing nanoparticles within this size range. This limitation is particularly pressing in view of several recent studies that show the importance of nanoparticle shape in regulating their cellular uptake and in vivo transport,[4–6] as demonstrated for the uptake of gold nanoparticles by macrophages,[7] for margination dynamics of nanoparticles in blood vessels,[6] and for the tissue distribution and circulation stability and thus drug delivery efficiency of organic and inorganic nanoparticles.[5, 8] We note that none of these shaped nanoparticles have been used to package and deliver plasmid DNA.Here, we report a new method for tuning plasmid DNA nanoparticles by varying solvent polarity during the condensation of DNA with PEG-b-polyphosphoramidate (PPA)[9, 10](Fig. 1). Upon separately dissolving the copolymer (Fig. S1 and Table S1) and plasmid DNA in dimethylformamide (DMF)–water mixtures at fixed volumetric ratios and mixing the two solutions at a predetermined copolymer-to-DNA ratio to achieve effective DNA condensation,[11] we have observed a striking variation in morphology (Fig. 1b–e). Micelles formed in pure water assumed a mixture of long worm-and ring-like morphologies (Fig. 1b). In a 3: 7 (v/v) DMF–water mixture, a small fraction of spherical and rod-like micelles appeared among the dominant worm-like structures (Fig. 1c) with lengths shorter than those observed in water. When the DMF/water volumetric ratio was increased to 5: 5, more than 90% of the micelles adopted a uniform, rod-like morphology (Fig. 1d) with a diameter of 24±3 nm and a length of 70±10 nm. Additionally, we observed a small population of spherical micelles with a diameter of 41±7 nm. Further increase in the DMF/water volumetric ratio to 7: 3 led to formation of highly uniform spherical micelles with a diameter of 40±5 nm (Fig. 1e). These structures were confirmed using cryogenic TEM imaging (Fig. S2). This method of generating DNA-compacting micelles with different shapes is not limited to DMF as a co-solvent; we have successfully prepared a series of analogous micelles using dimethyl sulfoxide (DMSO)–water solvent mixtures (Fig. S3).
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影响因子：
5.5
作者：
Guo, L;Luijten, E
通讯作者：
Luijten, E
影响因子：
8.6
作者：
Hsiao, Pai-Yi;Luijten, Erik
通讯作者：
Luijten, Erik
DOI：
10.1073/pnas.0705898104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Sanders, Lori K.;Xian, Wujing;Wong, Gerard C. L.
通讯作者：
Wong, Gerard C. L.
金纳米颗粒的几何形状和表面特征会影响其生物分布和巨噬细胞的吸收。
DOI：
10.1016/j.ejpb.2010.11.010
发表时间：
2011-04
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
--
作者：
Arnida;Janát-Amsbury MM;Ray A;Peterson CM;Ghandehari H
通讯作者：
Ghandehari H
影响因子：
29.4
作者：
Jiang, Xuan;Zheng, Yiran;Chen, Hunter H.;Leong, Kam W.;Wang, Tza-Huei;Mao, Hai-Quan
通讯作者：
Mao, Hai-Quan