使用Photoredox催化剂蠕虫状胶束的简便合成可见光介导的分散聚合
Summary
This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.
Abstract
Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (λ = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.
Introduction
非球形（和其他）纳米颗粒形态的合成历来使用开始具有良好定义的两亲二嵌段（或嵌段）共聚物的合成和纯化的多步自组装过程完成。其中最常见的自组装技术是由Eisenberg的在20世纪90年代普及并涉及两亲性嵌段共聚物在普通溶剂为两种聚合物嵌段，随后缓慢加入溶剂选择性为块1〜3之一的溶解。作为添加的选择性溶剂（通常为水）中，嵌段共聚物经受自组装以形成聚合物纳米颗粒。最终形态（或形态的混合物）的纳米粒子是由大量的因素，例如各聚合物嵌段，加水的速度与共用的溶剂的性质的相对长度来确定。然而，这种方法一般只允许生产nanopar的ticles在相对 低的固体含量（小于1重量％），因此限制了它的实际的可扩展性4。此外，“中间”相，例如蠕虫状胶束可再现形成可以由于窄的范围的，以稳定这种非球形形态5所需的参数是困难的。
聚合诱导的自组装（PISA）的方法通过利用聚合过程本身来驱动的自组装的原位允许纳米颗粒合成在高得多的固体含量部分地解决了上述艾森伯格方法的缺点（通常为10-30重量％）6 -8。在一个典型的PISA方法中，活性聚合过程用于链延伸的溶剂可溶的大分子引发剂（或宏CTA）与单体是在反应介质中最初可溶，但形成不溶性聚合物。 PISA的方法已被用于通过系统性测试数前的合成蠕虫状胶束 perimental参数，并使用详细的相图作为合成“路线图”5,9。
尽管他们的具有挑战性的合成，存在蠕虫状纳米颗粒由于它们相对于它们的球形同行有趣的性质极大的兴趣。例如，我们已经证明，使用PISA方法合成的装载药物短期和长期的蠕虫状胶束具有体外细胞毒性显著更高相比球状胶束或囊泡10。他人在体内模型11中所示的纳米粒子的纵横比和血液循环时间之间的相关性。其他人已经表明蠕虫状纳米粒子的使用适当的PISA方法合成产生一个宏观凝胶由于纳米颗粒长丝的纳米级纠缠。这些凝胶表现出作为由于其热可逆溶胶-凝胶行为12灭菌凝胶的潜力。
内容】“>该协议描述了在聚合过程中简单地观察该溶液的粘度允许原位监测蠕虫状胶束的形成的方法。相似的蠕虫状胶束凝胶的先前的研究已经表明，高于临界温度时，这些纳米颗粒经受可逆蜗杆球面过渡，因此形成在高温下自由流动的分散体。迄今为止，这些系统已经利用一个热敏感偶氮化合物以引发受控聚合13,14等凝胶化可能不容易在这些系统中观察到热聚合。从这些研究中，有人推测在较低温度下合成PISA衍生的纳米颗粒可允许原位这种凝胶行为观察。最近我们报道了用一个浅显的室温光聚合技术来调解PISA过程中产生的纳米粒子不同形貌15。这里，可视化协议是由在聚合过程中观察溶液的粘度行为呈现为蠕虫状胶束的再生合成。该分散体聚合反应的进行很容易地利用市售的发光二极管（LED）（λ= 460纳米，0.7毫瓦/厘米2）。
Protocol
Representative Results
Discussion
这种可视化协议表明仅仅通过观察凝胶状行为的发作，监测蠕虫状胶束的形成的能力。这种方法的效用在于以监测，相较于其他的方法在聚合过程中蠕虫形成的能力。可使用两种市售的单体（OEGMA和BzMA的）的两阶段的聚合，得到的自组装POEGMA- b -PBzMA两亲嵌段共聚物来执行此过程。
这里应注意的是，具有不同的反应器几何形状，光强度等 ，相对于与图2</stro…
Disclosures
The authors have nothing to disclose.
Acknowledgements
CB is thankful for his Future Fellowship from Australian Research Council (ARC-FT12010096) and UNSW Australia.
Materials
| 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPADB) | Sigma-Aldrich | 722995-5G | |
| Oligo(ethylene glycol) methyl ether methacrylate (OEGMA) | Sigma-Aldrich | 447935-500ML | Average Mn 300, contains 100 ppm MEHQ as inhibitor, 300 ppm BHT as inhibitor |
| 2,2′-Azobis(2-methylpropionitrile) (AIBN) | Sigma-Aldrich | ||
| Ru(bpy)3Cl2.6H2O | Sigma-Aldrich | 544981-1G | |
| Benzyl methacrylate (BzMA) | Sigma-Aldrich | 409448-1L | Contains monomethyl ether hydroquinone as inhibitor |
| Aluminium oxide (basic) | Chem-Supply Pty Ltd Australia | AL08371000 | |
| 95% Ethanol (EtOH) | Sucrogen Bio Ethanol | 80889 | |
| Acetonitrile (MeCN) | Chem-Supply Pty Ltd Australia | RP1005-G2.5L | |
| Tetrahydrofuran (THF) | Chem-Supply Pty Ltd Australia | TA011-2.5L | |
| Petroleum Spirits (40-60oC) | Chem-Supply Pty Ltd Australia | PA044-2.5L | |
| Diethyl Ether | Chem-Supply Pty Ltd Australia | EA0362.5L | |
| Dimethylacetamide (DMAc) | VWR International Australia | ALFA22916.M1 | For GPC analysis |
| Pasteur pipettes (230 mm) | Labtek | 355.050.503 | |
| Glass beakers | Labtek | 025.01.902 (2L)/ 2110654 (1L) | 2L beaker is for attaching LED strips to form the circular reactor |
| Commercial LED strip | EcoLab | n/a | λ = 460 nm, 4.8 W/m |
| 4 mL Glass Vials | Labtek | APC502214B | |
| 0.9 mL Quartz Cuvette | Starna Scientific Ltd | 21/Q/2 | |
| Needle (0.8 mm x 38 mm) | Beckton Dickson | 302017 | For deoxygenating reactions |
| Needle (0.8 mm x 120 mm) | B Braun Australia | 4665643 | For deoxygenating reactions |
| Sleeve stopper septa (rubber septum) | Sigma-Aldrich | z564680/z564702 | |
| Stirring hotplates | VWR International Australia/In Vitro Technologies | 97018-488/RADRR91200 | |
| Vortex mixer | VWR International Australia | 412-0098 | |
| Vacuum oven | In Vitro Technologies | MEMVO200 |
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