How To Tune the Gene Delivery and Biocompatibility of Poly(2-(4-aminobutyl)-2-oxazoline) by Self- and Coassembly.
How To Tune the Gene Delivery and Biocompatibility of Poly(2-(4-aminobutyl)-2-oxazoline) by Self- and Coassembly.
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DOI：
10.1021/acs.biomac.7b01535
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发表时间：
2017-12
影响因子：
6.2
通讯作者：
M. N. Leiske;Fabian H. Sobotta;Friederike Richter;S. Hoeppener;Johannes C. Brendel;Anja Traeger;U. Schubert
中科院分区：
文献类型：
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作者：
M. N. Leiske;Fabian H. Sobotta;Friederike Richter;S. Hoeppener;Johannes C. Brendel;Anja Traeger;U. Schubert
尽管阳离子聚合物在基因转染方面具有很好的应用前景，但其作为非病毒载体的毒性和有限的效率是其广泛应用的主要障碍。例如，已知聚（乙烯亚胺）（PEI）中的大量阳离子电荷在其转染效率方面是有利的，但同时具有高毒性。因此，需要对电荷进行有效的屏蔽以使毒性效应最小化。在这项研究中，我们使用一个简单的混合胶束的方法来优化所需的电荷密度，有效的DNA复合物的形成，并通过使用生物相容性聚合物，以尽量减少毒性。详细地说，我们共组装混合的聚（2-恶唑啉）纳米结构（直径100 nm）组成的疏水阳离子嵌段共聚物（P（NonOx 52-b-AmOx 184））和疏水亲水隐形嵌段共聚物（P（EtOx 155-b-NonOx 76）的比例为0，20，40，60，80，和100重量% P（NonOx 52-b-AmOx 184）。所有的胶束与阳离子聚合物表现出非常好的DNA结合效率和解离能力，而生物和血液相容性的提高与EtOx含量。通过共聚焦激光扫描显微镜和流式细胞仪分析显示，增强细胞摄取，转染能力，和生物相容性的所有制备的胶束复合物相比，AmOx均聚物。具有80或100重量%的胶束复合物显示出与PEI类似的转染效率，而细胞活力显著更高（80至90%，与PEI的60%相比）。
Despite their promising potential in gene transfection, the toxicity and limited efficiency of cationic polymers as nonviral vectors are major obstacles for their broader application. The large amount of cationic charges, for example, in poly(ethylene imine) (PEI) is known to be advantageous in terms of their transfection efficiency but goes hand-in-hand with a high toxicity. Consequently, an efficient shielding of the charges is required to minimize toxic effects. In this study, we use a simple mixed-micelle approach to optimize the required charge density for efficient DNA complex formation and to minimize toxicity by using a biocompatible polymer. In detail, we coassembled mixed poly(2-oxazoline) nanostructures ( d ≈ 100 nm) consisting of a hydrophobic-cationic block copolymer (P(NonOx52- b-AmOx184)) and a hydrophobic-hydrophilic stealth block copolymer (P(EtOx155- b-NonOx76) in ratios of 0, 20, 40, 60, 80, and 100 wt % P(NonOx52- b-AmOx184). All micelles with cationic polymers exhibited a very good DNA binding efficiency and dissociation ability, while the bio- and hemocompatibility improved with increasing EtOx content. Analytics via confocal laser scanning microscopy and flow cytometry showed an enhanced cellular uptake, transfection ability, and biocompatibility of all prepared micelleplexes compared to AmOx homopolymers. Micelleplexes with 80 or 100 wt % revealed a similar transfection efficiency as PEI, while the cell viability was significantly higher (80 to 90% compared to 60% for PEI).