电活性聚合物纳米粒子参展光热特性
Summary
A protocol is presented for the synthesis and preparation of nanoparticles consisting of electroactive polymers.
Abstract
A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).
Introduction
电活性聚合物在电场的存在下改变它们的属性（颜色，导电性，反应性， 体积等）。的快速切换时间，可调谐性，耐久性和电活性聚合物的重量轻的特性，导致许多提出的应用，包括可替代能源，传感器，电致变色，和生物医学器件。电活性聚合物是灵活，重量轻的电池和电容器的电极可能是有用的。1应用电活性聚合物的电致变色器件包括炫光系统用于建筑物和汽车，太阳镜，保护眼镜，光学存储 设备，和智能纺织品。2-5智能窗可以通过阻止光点播的特定波长，保护家庭和汽车的内部降低能源需求。智能纺织品可以在服装被用来帮助防止紫外线辐射。6电活性聚合物有ALSö开始在医疗设备中使用。间在生物医学装置中使用电活性聚合物，聚吡咯（聚吡咯），聚苯胺（PANI），和聚（3,4-亚乙基）（PEDOT）是最常见的。例如，这些类型的聚合物通常用作在生物传感器装置的换能器7的应用在治疗递送也显示出前景。研究已经证实的药物和治疗性蛋白质的释放从电活性聚合物制备装置。8-12最近，电活性聚合物已经用作在光热疗法的治疗剂。13-15在光热疗法，光热剂必须吸收光，在不久的-红外（NIR）区域（〜700-900纳米），也被称为治疗窗，其中光具有穿透组织的最大深度，典型地高达1厘米。16,17在此范围内，生物生色团如血红蛋白，氧化血红蛋白，脂质和水几乎没有到没有吸收，使光线容易渗透。当光热剂吸收光在此治疗窗，所述光能转换为光热能量。
欧文和同事以前曾报道烷氧基取代的合成使用Negishi偶联该被双-苯EDOT单体。18 Negishi偶联为碳-碳键形成的优选方法。这个过程有许多优点，包括使用有机锌中间体，它们是毒性较低并趋向于具有更高的反应性比使用其它有机金属化合物。19,20有机锌化合物也与在有机卤化物一个宽范围的官能团相容。20在 Negishi偶联反应，有机卤化物和有机金属是通过使用钯（0）催化剂的耦合。20在这里所提出的工作，这种交叉偶联方法是利用在1,4-二烷氧基-2,5-二合成（ 3,4- ethylenedioxythienyl）benzeね（BEDOT-B（OR）2）的单体。这些单体然后可以很容易地聚合电化学或化学产生是有希望的候选用于生物医学应用中使用的聚合物。
常规方法制备的在生物医学应用水溶液胶体聚合物悬浮液通常包括本体聚合物，接着纳米沉淀或乳液溶剂蒸发技术。21,22为了生产聚纳米粒溶解（BEDOT-B（OR）2） ，自底向上的方法在这里展示，其中纳米颗粒通过原位乳液聚合合成。乳液聚合是一个过程，是易于扩展，并且是相对快速的方法制备的NP。使用乳液聚合以产生其他电活性聚合物的纳米颗粒22的研究已报道了聚吡咯和PEDOT。15,23,24 PEDOT纳米颗粒，例如，使用喷雾乳液p与编制olymerization 24这种方法是难以再现，并通常产生较大的，微米尺寸的颗粒。在这篇文章中所描述的协议探讨采用了下拉式超声法可重复制作100纳米的聚合物纳米颗粒。
在这个协议中，电活性聚合物适合吸收光在近红外区域类似于先前报道的聚（BEDOT-B（OR）2） 合成和表征证明在电致变色器件和作为PTT代理他们的潜力。首先，该协议用于经由Negishi偶联单体的合成进行说明。使用NMR和紫外 – 可见 – 近红外光谱的单体的特征在于。的NP胶体悬浮液通过氧化乳液聚合在水性介质中制备还描述。该程序是基于先前由Han等被施加到不同的单体描述的两步乳液聚合法。两表面活性剂体系用来控制对NP的单分散性。一个细胞活力测定是用来评估纳米颗粒的细胞相容性。最后，这些纳米粒子作为PTT换能器的电势被证明通过用近红外激光照射。
Protocol
Representative Results
Discussion
在这项工作中，电活化聚合物纳米粒子已被合成作为潜在的PTT剂用于癌症治疗。该纳米颗粒的制备方法进行说明，首先，接着通过乳液聚合单体的合成。在使用电活性聚合物如EDOT和吡咯纳米颗粒的制备已经描述之前，阐述的聚合物纳米颗粒的制备方法起始与独特扩展共轭单体，这表明该方法可以扩展到更大，更复杂的单体。
两种不同的路线是必要的，合成的二烷氧基苯单体?…
Declarações
The authors have nothing to disclose.
Acknowledgements
这项工作是部分资金由得克萨斯州的新兴科技基金（启动到TB），德克萨斯州立大学的研究增强计划，得克萨斯州立大学博士研究奖学金（到TC），美国国家科学基金会合作研究和教育材料（PREM， DMR-1205670），卫生韦尔奇基金会（AI-0045），和美国国家研究院（R01CA032132）。
Materials
| 2 mm diameter platinum working electrode | CH Instruments | CH102 | Polished using very fine sandpaper |
| 3,4-ethylenedioxythiophene | Sigma-Aldrich | 483028 | Purified by vacuum distillation |
| 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) 98% | Alfa Aesar | L11939 | |
| 505 Sonic Dismembrator | Fisher Scientific™ | FB505110 | 1/8 “ tip and rated at 500 watts |
| 808 nm laser diode | ThorLabs | L808P1WJ | Rated at 1 W |
| Acetonitrile anhydrous 99% | Acros | 61022-0010 | |
| Avanti J-26 XPI | Beckman Coulter | 393127 | |
| Bromohexane 98% | MP Biomedicals | 202323 | |
| Dialysis (100,000) MWCO | SpectrumLabs | G235071 | |
| Dimethyl sulfoxide 99% (DMSO) | BDH | BDH1115 | |
| Dimethylformamide anhydrous (DMF) 99% | Acros | 326870010 | |
| Dodecyl benzenesulfonate (DBSA) | TCI | D0989 | |
| Dulbecco’s modified eagle medium (DMEM) | Corning | 10-013 CV | |
| EMS 150 TES sputter coater | Electron Microscopy Sciences | ||
| Ethanol (EtOH) 100% | BDH | BDH1156 | |
| ethyl 4-bromobutyrate (98%) | Acros | 173551000 | |
| Ethyl acetate 99% | Fisher | UN1173 | |
| Fetal bovine serum (FBS) | Corning | 35-010-CV | |
| Helios NanoLab 400 | FEI | ||
| Hexane | Fisher | H306-4 | |
| Hydrochloric acid (HCl) | Fisher | A142-212 | |
| Hydroquinone 99.5% | Acros | 120915000 | |
| Hydrozine anhydrous 98% | Sigma-Aldrich | 215155 | |
| Indium tin oxide (ITO) coated galss | Delta Technologies | CG-41IN-CUV | 4-8 Ω/sq |
| Iron chloride 97% FeCl3 | Sigma-Aldrich | 157740 | |
| Magnesium sulfate (MgSO4) | Fisher | 593295 | Dried at 100 oC |
| SKOV-3 | ATCC | HTB-26 | |
| Methanol | BDH | BHD1135 | |
| n-Butlithium (2.5 M) | Sigma-Aldrich | 230707 | Pyrophoric |
| Poly(styrenesulfonate-co-malic acid) (PSS-co-MA) 20,000 MW | Sigma-Aldrich | 434566 | |
| Potassium carbonate | Sigma-Aldrich | 209619 | Dried at 100 oC |
| Potassium hydroxide | Alfa Aesar | A18854 | |
| Potassium iodide | Fisher | P410-100 | |
| RO-5 stirplate | IKA-Werke | ||
| SC4000 IR camera | FLIR | ||
| Synergy H4 Hybrid Reader | Biotek | ||
| Tetrabutylammonium perchlorate (TBAP) 99% | Sigma-Aldrich | 3579274 | Purified by recrystallization in ethyl acetate |
| Tetrahydrofuran anhydrous (THF) 99% | Sigma-Aldrich | 401757 | |
| tetrakis(triphenylphosphine) palladium(0) |
Sigma-Aldrich | 216666 | Moisture sensitive |
| Thermomixer | Eppendorf | ||
| USB potentiostat/galvanostat | WaveNow | AFTP1 | |
| Zetasizer Nano Zs | Malvern | Optical Arrangment 175o | |
| Zinc chloride (1 M) ZnCl2 | Acros | 370057000 |
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