This research was supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canada Research Chairs Program, and Simon Fraser University. This work made use of 4D LABS shared facilities supported by the Canada Foundation for Innovation (CFI), British Columbia Knowledge Development Fund (BCKDF) and Simon Fraser University.

1.合成了NaYF 4 /镱3+ / ER 3+上变频纳米粒子（UCNP）的<ol><li>设置该装置如下: <ol><li>将250毫升的加热套定期搅拌板和插套到热电偶。 </li><li>放置一个250ml圆底烧瓶配备有磁力搅拌棒上的加热罩以适当的夹紧。 </li><li>附加一个空气适配器到圆底烧瓶的左颈部和该空气适配器连接到的Schlenk线与塑料管。 </li><li>附加的玻璃适配器到圆底烧瓶的右颈部和固定温度计适配器到玻璃适配器。将温度探针插入通过温度计适配器烧瓶中，将其插入热电偶。 </li><li>附加一个蒸馏头到圆底烧瓶的中间颈部。放置在蒸馏头的顶部的止动。连接头至冷凝器，然后通过真空distillat离子适配器和50毫升圆底烧瓶中。真空蒸馏适配器连接，通过塑料管鼓泡。 </li></ol></li><li>权衡1.17克（3.9毫摩尔）的乙酸钇，0.439克的镱乙酸和0.0727克的铒乙酸（0.1毫摩尔），并将其放置在反应圆底烧瓶中。 </li><li>加入30 ml的油酸和75ml十八烯向烧瓶用量筒。 </li><li>冲洗，用5毫升甲醇，以确保没有油酸和十八碳烯粘到反应烧瓶的侧面圆底烧瓶内的反应的一侧。 </li><li>反应烧瓶连接到双歧管的Schlenk线，并打开相应的阀，以保持反应烧瓶连接到氮气管线。 </li><li>打开热电偶，设定温度至80℃，并且系统逐渐加热到该温度。在80℃和所有的起始原料都溶解后，除去加热套和使反应冷却到30℃。 </li><li>当温度达到30℃时，取下蒸馏头，从左侧颈切换空气适配器到中间颈部和封闭左颈部用塞子。慢慢转动阀上的Schlenk线从氮气管线到真空管引入真空到反应烧瓶中。所有的低沸点组分将在从此时反应拉出。 </li><li>当溶液停止鼓泡，，升温至115℃以5℃/分钟的速度移动。 </li><li>一旦温度达到115℃，保持此温度15分钟，然后取出加热套和冷却该反应至50℃。之后，快速切换设置回原始形式通过重新连接该蒸馏头到中间颈部和空气适配器向左侧头部。 </li><li>在冷却过程中称出0.74克的NaOH（12.5毫摩尔）和0.50克的NH 4 F（20.0毫摩尔），并溶解它们在50毫升甲醇中通过超声处理。 </li><li>超声处理后，将溶液倒入圆底烧瓶中的反应和漂洗烧瓶的侧面，用5毫升甲醇。 </li><li>离开溶液在50℃下搅拌30分钟。 </li><li>提高温度至75℃，蒸馏甲醇。 </li><li>在蒸馏过程中，空收集瓶必要时。后蒸馏完成后，加热反应至300℃在氮气保护下尽可能快。 </li><li>一旦温度达到300℃，保持这个温度1小时。如果需要的话，用铝箔覆盖的设置，以帮助保持温度。然后除去热源，并允许该反应冷却到室温。 </li><li>一旦它被冷却到室温，平分该溶液分为三个离心管（50ml试管，每每个管大约35个ml的溶液），和顶部上的管，以50 ml的规模使用无水乙醇。离心机所有的t他铝管3,400 XG 15分钟。离心后，将UCNPs应在管的侧面观察，为白色沉淀物。 </li><li>弃去上清液并再分散UCNPs粒料在己烷（7.5 ml的每各管己烷），然后补足管，用乙醇至50ml刻度的。离心管再次在3400×g离心15分钟。 </li><li>一旦离心完成后，弃去上清液并再分散的固体UCNPs在30ml 氯仿中供进一步使用。 </li></ol> 2.装配水分散性Nanoassemblies含有有机染料分子和上变频纳米粒子<ol><li>溶解的聚（苯乙烯-马来中高音酐）25毫克（0.0147毫摩尔）（PSMA）在3ml 氯仿的成闪烁小瓶配有磁力搅拌棒。这个量是经过多次试验优化的数量。 </li><li>添加上变频的250微升（47毫克/毫升）的纳米颗粒的氯仿贮存液至scintillation小瓶。 </li><li>盖上小瓶，并将其放置在磁力搅拌板上，搅拌该溶液在室温下搅拌2小时。 </li><li>称取聚醚160毫克（0.0773毫摩尔）胺2070和溶解在1毫升氯仿中。然后用移液管一次性添加该溶液至闪烁瓶中。该解决方案将变成浅黄色，表示聚醚胺2070与上PSMA酸酐基团反应。 </li><li>继续搅拌该溶液在室温下过夜。 </li><li>测量的有机染料分子的数量适当然后分配入闪烁小瓶中一次性，搅拌1小时，所得溶液。 <ol><li>对于样本TPP-NP（nanoassembly含聚合物外壳，四苯基卟啉和上变频纳米颗粒），直接增加1毫克四苯基卟啉的闪烁瓶中。对于样本DAE-UCNP（nanoassembly含聚合物外壳，二芳基乙烯分子和上变频纳米粒子多个），二芳基乙烯的每个分子的数量是2×10 -7摩尔。添加两个二芳基乙烯分子导入反应溶液中。该卷两个二芳基乙烯分子是:DAE-1O（1.8毫米），111微升和DAE-20（1.6毫米），125微升。 </li></ol></li><li>在减压下除去，在CHCl 3溶剂使用旋转蒸发器，再加入3 ml的0.001 M个NaOH水溶液（pH值≈11）的闪烁瓶中，然后超声处理小瓶直到乳状悬浮液形成。 </li><li>将小瓶背面旋转蒸发器上，并小心地除去剩余氯仿 ，直到悬浮液变成透明溶液。 </li><li>从闪烁瓶中将该溶液转移到2个1.5毫升锥形离心管中，然后离心该溶液在20600×g离心25分钟。 </li><li>弃去上清液，然后共3 ml的去离子H 2 O的的添加到两管（每管1.5毫升）中，超声处理管再分散粒料在去离子H 2 O </li><li>再次离心两管在20600×g离心25分钟。 </li><li>弃去上清液，然后共3毫升去离子H 2 O的的添加到两管（每管1.5毫升）中。超声处理管再分散颗粒在去离子H 2 O </li><li>通过0.2μm注射器过滤器过滤该水性分散体的纳米颗粒样品以获得用于进一步测试的最终样品。 </li></ol>

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The authors have nothing to disclose.

根据此协议中合成的纳米颗粒具有从20至25纳米的中心在左右22.5纳米。-26,27-它们可以被分类为球形颗粒与α-NaYF 4主晶格结构的尺寸分布。还有在这个协议中的两个关键步骤。在UCNP合成，关键的是要维持加热温度和时间尽可能精确，以保证颗粒尺寸分布窄。同时加入的NaOH和NH 4 F一起在反应没有产生纳米颗粒的良好分布尺寸和良好的形态的开头添加镧系元素离子。加入的NaOH?...

今天，仍然是一个迫切需要开发新型生物成像剂。许多新的荧光探针已经有案可稽1-6然而，在图像分辨率实质性改进仍然是一个挑战。7的一个实际方法是直接调制"光"发射状态和一个"暗"淬火状态之间的荧光探针。 8-12这种特殊方法已被应用到开发的技术，如受激发射损耗（STED）显微镜13和随机光学重构显微术（STORM）14 来调制荧光另一种方法是为耦合光响应性的发色团一起用荧光探针。15,16切换两种异构体，即只有一个异构体可以作为有效的能量转移受体之间的光响应发色团，允许控制从第荧光猝灭通过荧光共振能量转移（FRET）等机制Ë探头。的结果是创建的发射状态，并且可以由光响应发色团，以不同波长的光的曝光交替急冷状态。 光响应二芳基乙烯的发色团可以为无色开环异构体和着色环封闭异构体照射时，用紫外和可见光之间发生可逆切换。17-19的两种异构体的闭环异构体的化妆和可调谐吸收光谱的热稳定性二芳基乙烯非常好的候选者可控的FRET受体20-23的镧系元素掺杂的NaYF 4纳米颗粒上变换是用于生物成像是有用的。24这些纳米颗粒吸收的近红外光并发光，在可见光谱的几个区域。荧光调制通过组合光响应二芳基乙烯的发色团和纳米颗粒的例子已预先viously报告由我们的组25-27然而，在每个实施例中描述的系统需要一个额外的合成修饰的二芳基乙烯附着到纳米颗粒的表面，其中复杂更多样化的系统的开发。 在这里我们展示了一个简单的"即插即玩"的方法准备使用自组装策略水分散性有机染料分子和光响应上变频纳米粒子。聚合物的选择;聚（苯乙烯-马来中高音酐）和聚醚胺2070同时提供疏水性和亲水性的环境。的聚合物帮助疏水部分以保持正常的水不溶性有机分子，并上变频纳米颗粒一起，而该聚合物的亲水区是用于保持水溶解度的关键。首先，我们将展示由热核方法合成上变频纳米粒子。然后，我们将证明豪瓦特的有机分子，并上变频纳米颗粒的聚合物壳的疏水区内包封和保持稳定在水介质中通过简单地共同搅拌该升压变换纳米颗粒，聚合物和不同的有机染料分子的溶液，接着通过一种方便的处理过程。我们还演示了如何调制使用外部光线照射组件的荧光发射。我们预计，采用这种"即插即用"的方法，使水分散性nanoassemblies将继续扩大范围。

<table><tbody><tr><td>Yttrium acetate</td><td>Sigma</td><td>326046</td><td>Yttrium(III) acetate hydrate</td></tr><tr><td>Ytterbium acetate</td><td>Sigma</td><td>544973</td><td>Ytterbium(III) acetate hydrate</td></tr><tr><td>Erbium acetate</td><td>Sigma</td><td>325570</td><td>Erbium(III) acetate hydrate</td></tr><tr><td>Oleic acid</td><td>Sigma</td><td>75096</td><td>analytical standard</td></tr><tr><td>Octadecene</td><td>Sigma</td><td>O806</td><td>Technical grade</td></tr><tr><td>NaOH</td><td>Sigma</td><td>S5881</td><td>reagent grade</td></tr><tr><td>NH&lt;sub&gt;4&lt;/sub&gt;F</td><td>Sigma</td><td>216011</td><td>ACS reagent</td></tr><tr><td>Poly(styrene-co-maleic anhydride)</td><td>Sigma</td><td>442399</td><td>Average Mn = 1700</td></tr><tr><td>JeffAmine 2070</td><td>Huntsman</td><td>M-2070</td><td></td></tr><tr><td>Varian Carry 300</td><td>Agilent</td><td></td><td></td></tr><tr><td>JDSU NIR laser</td><td>JSDU</td><td>L4-9897510-100M</td><td>980 nm diode laser</td></tr></tbody></table>

a 'plug and play' method to create water-dispersible nanoassemblies containing an amphiphilic polymer, organic dyes and upconverting nanoparticles

In this protocol, we first describe a procedure to synthesize lanthanide doped upconverting nanoparticles (UCNPs). We then demonstrate how to generate amphiphilic polymers in situ, and describe a protocol to encapsulate the prepared UCNPs and different organic dye molecules (porphyrins and diarylethenes) using polymer shells to form stable water-dispersible nanoassemblies. The nanoassembly samples containing both the UCNPs and the diarylethene organic dyes have interesting photochemical and photophysical properties. Upon 365 nm UV irradiation, the diarylethene group undergoes a visual color change. When the samples are irradiated with visible light of another specific wavelength, the color fades and the samples return to the initial colorless state. The samples also emit visible light from the UCNPs upon irradiation with 980 nm near-infrared light. The emission intensity of the samples can be tuned through alternate irradiation with UV and visible light. Modulation of fluorescence can be performed for many cycles without observable degradation of the samples. This versatile encapsulation procedure allows for the transfer of hydrophobic molecules and nanoparticles from an organic solvent to an aqueous medium. The polymer helps to maintain a lipid-like microenvironment for the organic molecules to aid in preservation of their photochemical behavior in water. Thus this method is ideal to prepare water-dispersible photoresponsive systems. The use of near-infrared light to activate upconverting nanoparticles allows for lower energy light to be used to activate photoreactions instead of more harmful ultraviolet light.

吸收光谱和荧光光谱采集样品DAE-UCNP。吸收光谱被用于封闭二芳基乙烯的发色团和上变频纳米颗粒之间比较光谱重叠。样品（两者TPP-UCNP和DAE-UCNP）的照片也被包括在内以证明有机染料分子和上变频纳米颗粒，其位于水相中的两亲聚合物壳中成功封装。光化学和荧光的调制也显示出由在不同的光源的样品照明。 化学理论"相似相溶"解释了为什么当在氯仿中卟啉或UCNPs的等分试样?...

Watch this Scientific Journal Video about A 'Plug and Play' Method to Create Water-dispersible Nanoassemblies Containing an Amphiphilic Polymer, Organic Dyes and Upconverting Nanoparticles at JoVE.com

A 'Plug and Play' Method to Create Water-dispersible Nanoassemblies Containing an Amphiphilic Polymer, Organic Dyes and Upconverting Nanoparticles

Organic dye molecules and oleic acid coated upconverting nanoparticles are not water-soluble. This protocol describes a &#8216;plug and play&#8217; method that enables the transfer of organic dye molecules and upconverting particles from their initial hydrophobic solvent to water.

A&#39;即插即用&#39;的方法来创建水分散性Nanoassemblies包含两亲聚合物，有机染料和上变频纳米粒子

In this protocol, we first describe a procedure to synthesize lanthanide doped upconverting nanoparticles (UCNPs). We then demonstrate how to generate ...

a-plug-play-method-to-create-water-dispersible-nanoassemblies

Universidad de Cartagena UDEC

Research

JoVE Journal

Chemistry

9.8K 次观看.  Simon Fraser University. Organic dye molecules and oleic acid coated upconverting nanoparticles are not water-soluble. This protocol describes a ‘plug and play’ method that enables the transfer of organic dye molecules and upconverting particles from their initial hydrophobic solvent to water. 

视频: A 'Plug and Play' Method to Create Water-dispersible Nanoassemblies Containing an Amphiphilic Polymer, Organic Dyes and Upconverting Nanoparticles

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

For aqueous based supramolecular polymers, the simultaneous control over shape, size and stability is very difficult1. At the same time, the ability to do so is highly important in view of a number of applications in functional soft matter including electronics, biomedical engineering, and sensors. In the past, successful strategies to control the size and shape of supramolecular polymers typically focused on the use of templates2,3, end cappers4 or selective solvent techniques5. 
Here we disclose a strategy based on self-assembling discotic amphiphiles that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing electrostatic repulsive interactions on the hydrophilic rim and attractive non-covalent forces within the hydrophobic core of the polymerizing building block, we manage to create small and discrete spherical objects6,7. Increasing the salt concentration to screen the charges induces a sphere-to-rod transition. Intriguingly, this transition is expressed in an increase of cooperativity in the temperature-dependent self-assembly mechanism, and more stable aggregates are obtained. 
For our study we select a benzene-1,3,5-tricarboxamide (BTA) core connected to a hydrophilic metal chelate via a hydrophobic, fluorinated L-phenylalanine based spacer (Scheme 1). The metal chelate selected is a Gd(III)-DTPA complex that contains two overall remaining charges per complex and necessarily two counter ions. The one-dimensional growth of the aggregate is directed by &pi;-&pi; stacking and intermolecular hydrogen bonding. However, the electrostatic, repulsive forces that arise from the charges on the Gd(III)-DTPA complex start limiting the one-dimensional growth of the BTA-based discotic once a certain size is reached. At millimolar concentrations the formed aggregate has a spherical shape and a diameter of around 5 nm as inferred from 1H-NMR spectroscopy, small angle X-ray scattering, and cryogenic transmission electron microscopy (cryo-TEM). The strength of the electrostatic repulsive interactions between molecules can be reduced by increasing the salt concentration of the buffered solutions. This screening of the charges induces a transition from spherical aggregates into elongated rods with a length &gt; 25 nm. Cryo-TEM allows to visualise the changes in shape and size. In addition, CD spectroscopy permits to derive the mechanistic details of the self-assembly processes before and after the addition of salt. Importantly, the cooperativity -a key feature that dictates the physical properties of the produced supramolecular polymers- increases dramatically upon screening the electrostatic interactions. This increase in cooperativity results in a significant increase in the molecular weight of the formed supramolecular polymers in water.

The goal of this experiment is to determine and control the size, shape and stability of self-assembled discotic amphiphiles in water. For aqueous based supramolecular polymers such level of control is very difficult. We apply a strategy using both repulsive and attractive interactions. The experimental techniques applied to characterize this system are broadly applicable.

控制的大小，形状和稳定性超分子聚合物在水

For aqueous based supramolecular polymers, the simultaneous control over shape, size and stability is very difficult1. At the same time, the ability to do ...

科研

工程学

A Technique to Functionalize and Self-assemble Macroscopic Nanoparticle-ligand Monolayer Films onto Template-free Substrates

This protocol describes a self-assembly technique to create macroscopic monolayer films composed of ligand-coated nanoparticles1,2. The simple, robust and scalable technique efficiently functionalizes metallic nanoparticles with thiol-ligands in a miscible water/organic solvent mixture allowing for rapid grafting of thiol groups onto the gold nanoparticle surface. The hydrophobic ligands on the nanoparticles then quickly phase separate the nanoparticles from the aqueous based suspension and confine them to the air-fluid interface. This drives the ligand-capped nanoparticles to form monolayer domains at the air-fluid interface.&#160; The use of water-miscible organic solvents is important as it enables the transport of the nanoparticles from the interface onto template-free substrates.&#160; The flow is mediated by a surface tension gradient3,4 and creates macroscopic, high-density, monolayer nanoparticle-ligand films.&#160; This self-assembly technique may be generalized to include the use of particles of different compositions, size, and shape and may lead to an efficient assembly method to produce low-cost, macroscopic, high-density, monolayer nanoparticle films for wide-spread applications.

A simple, robust and scalable technique to functionalize and self-assemble macroscopic nanoparticle-ligand monolayer films onto template-free substrates is described in this protocol.

一种技术，功能化和自组装纳米宏观 - 配体单层膜模板上无基材

This protocol describes a self-assembly technique to create macroscopic monolayer films composed of ligand-coated nanoparticles1,2. The simple, robust and ...

化学

Formulation of Diblock Polymeric Nanoparticles through Nanoprecipitation Technique

Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale (nanoparticles). Nanoparticles can be engineered in a precise fashion where their size, composition and surface chemistry can be carefully controlled. This enables unprecedented freedom to modify some of the fundamental properties of their cargo, such as solubility, diffusivity, biodistribution, release characteristics and immunogenicity. Since their inception, nanoparticles have been utilized in many areas of science and medicine, including drug delivery, imaging, and cell biology1-4. However, it has not been fully utilized outside of "nanotechnology laboratories" due to perceived technical barrier. In this article, we describe a simple method to synthesize a polymer based nanoparticle platform that has a wide range of potential applications. 
The first step is to synthesize a diblock co-polymer that has both a hydrophobic domain and hydrophilic domain. Using PLGA and PEG as model polymers, we described a conjugation reaction using EDC/NHS chemistry5 (Fig 1). We also discuss the polymer purification process. The synthesized diblock co-polymer can self-assemble into nanoparticles in the nanoprecipitation process through hydrophobic-hydrophilic interactions.
The described polymer nanoparticle is very versatile. The hydrophobic core of the nanoparticle can be utilized to carry poorly soluble drugs for drug delivery experiments6. Furthermore, the nanoparticles can overcome the problem of toxic solvents for poorly soluble molecular biology reagents, such as wortmannin, which requires a solvent like DMSO. However, DMSO can be toxic to cells and interfere with the experiment. These poorly soluble drugs and reagents can be effectively delivered using polymer nanoparticles with minimal toxicity. Polymer nanoparticles can also be loaded with fluorescent dye and utilized for intracellular trafficking studies. Lastly, these polymer nanoparticles can be conjugated to targeting ligands through surface PEG. Such targeted nanoparticles can be utilized to label specific epitopes on or in cells7-10.

This article describes a nanoprecipitation method to synthesize polymer-based nanoparticles using diblock co-polymers. We will discuss the synthesis of diblock co-polymers, the nanoprecipitation technique, and potential applications.

制定通过Nanoprecipitation技术嵌段聚合物纳米粒子

Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale ...

生物工程

Using Polystyrene-block-poly(acrylic acid)-coated Metal Nanoparticles as Monomers for Their Homo- and Co-polymerization

We present a template-free method for &#8220;polymerizing&#8221; nanoparticles into long chains without side branches. A variety of nanoparticles are encapsulated in polystyrene-block-poly(acrylic acid) (PSPAA) shells and then used as monomers for their self-assembly. Spherical PSPAA micelles upon acid treatment are known to assemble into cylindrical micelles. Exploiting this tendency, the core-shell nanoparticles are induced to aggregate, coalesce, and then transform into long chains. When more than one type of nanoparticles are used, random and block &#8220;copolymers&#8221; of nanoparticles can be obtained. Detailed procedures are reported for the PSPAA encapsulation of nanoparticles, homo- and co-polymerization of the core-shell nanoparticles, separation and purification of the resulting nanoparticle chains. Transformations of single-line chains into double- and triple-line chains are also presented. The synergy between the polymer shell and the embedded nanoparticles leads to an unusual chain-growth polymerization mode, giving long nanoparticle chains that are distinct from the products of the traditional step-growth aggregation process.

Using Polystyrene-block-polyacrylic acid-coated Metal Nanoparticles as Monomers for Their Homo- and Co-polymerization

We report protocols for &#8220;polymerizing&#8221; various types of polymer-encapsulated metal nanoparticles into long chains of &#8220;homo-&#8220; and &#8220;co-polymers&#8221;.

使用聚苯乙烯<em&gt;块</em&gt; - 聚（丙烯酸）涂层的金属纳米颗粒作为单体他们均聚物和共聚物聚合

We present a template-free method for &#8220;polymerizing&#8221; nanoparticles into long chains without side branches. A variety of nanoparticles are ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

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 (&#955; = 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.

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.

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

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Fabrication of Spherical and Worm-shaped Micellar Nanocrystals by Combining Electrospray, Self-assembly, and Solvent-based Structure Control

Micellar nanocrystals (micelles with encapsulated nanocrystals) have become an emerging major class of nanobiomaterials. We describe a method of fabricating micellar nanocrystals based on combining top-down electrospray, bottom-up self-assembly, and solvent-based structure control. This method involves first using electrospray to generate uniform ultrafine liquid droplets, each of which functions as a micro-reactor in which self-assembly reaction occurs forming micellar nanocrystals, with the structures (micelle shape and nanocrystal encapsulation) controlled by the organic solvent used. This method is largely continuous and produces high quality micellar nanocrystal products with an inexpensive structure control approach. By using a water-miscible organic solvent tetrahydrofuran (THF), worm-shaped micellar nanocrystals can be produced due to solvent-induced/facilitated micelle fusion. Compared with the common spherical micellar nanocrystals, worm-shaped micellar nanocrystals can offer minimized non-specific cellular uptake, thus enhancing biological targeting. By co-encapsulating multiple nanocrystals into each micelle, multifunctional or synergistic effects can be achieved. Current limitations of this fabrication method, which will be part of the future work, primarily include imperfect encapsulation in the micellar nanocrystal product and the incompletely continuous nature of the process.

The present work describes a method to fabricate micellar nanocrystals, an emerging major class of nanobiomaterials. This method combines top-down electrospray, bottom-up self-assembly, and solvent-based structure control. The fabrication method is largely continuous, can produce high quality products, and possesses an inexpensive means of structure control.

结合电喷雾、自组装和溶剂型结构控制制备球形和蜗杆状胶束纳米晶

Micellar nanocrystals (micelles with encapsulated nanocrystals) have become an emerging major class of nanobiomaterials. We describe a method of ...

Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock copolymers are produced by one of three techniques: thin film rehydration, solvent switching or polymerization-induced self-assembly, and produce only flexible, polydisperse cylinders. Crystallization-driven self-assembly (CDSA) is a method which can produce cylinders with these properties, by stabilizing structures of a lower curvature due to the formation of a crystalline core. However, the living polymerization techniques by which most core-forming blocks are formed are not trivial processes and the CDSA process may yield unsatisfactory results if carried out incorrectly. Here, the synthesis of cylindrical nanoparticles from simple reagents is shown. The drying and purification of reagents prior to a ring-opening polymerization of &#949;-caprolactone catalyzed by diphenyl phosphate is described. This polymer is then chain extended by methyl methacrylate (MMA) followed by N,N-dimethyl acrylamide (DMA) using reversible addition&#8722;fragmentation chain-transfer (RAFT) polymerization, affording a triblock copolymer that can undergo CDSA in ethanol. The living CDSA process is outlined, the results of which yield cylindrical nanoparticles up to 500 nm in length and a length dispersity as low as 1.05. It is anticipated that these protocols will allow others to produce cylindrical nanostructures and elevate the field of CDSA in the future.

Crystallization-driven self-assembly (CDSA) displays the unique ability to fabricate cylindrical nanostructures of narrow length distributions. The organocatalyzed ring-opening polymerization of &#949;-caprolactone and subsequent chain extensions of methyl methacrylate and N,N-dimethyl acrylamide are demonstrated. A living CDSA protocol that produces monodisperse cylinders up to 500 nm in length is outlined.

通过结晶驱动生物降解块共聚物的自组装合成单分散圆柱状纳米粒子

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock ...

Rapid, Scalable Assembly and Loading of Bioactive Proteins and Immunostimulants into Diverse Synthetic Nanocarriers Via Flash Nanoprecipitation

Nanomaterials present a wide range of options to customize the controlled delivery of single and combined molecular payloads for therapeutic and imaging applications. This increased specificity can have significant clinical implications, including decreased side effects and lower dosages with higher potency. Furthermore, the in situ targeting and controlled modulation of specific cell subsets can enhance in vitro and in vivo investigations of basic biological phenomena and probe cell function. Unfortunately, the required expertise in nanoscale science, chemistry and engineering often prohibit laboratories without experience in these fields from fabricating and customizing nanomaterials as tools for their investigations or vehicles for their therapeutic strategies. Here, we provide protocols for the synthesis and scalable assembly of a versatile non-toxic block copolymer system amenable to the facile formation and loading of nanoscale vehicles for biomedical applications. Flash nanoprecipitation is presented as a methodology for rapid fabrication of diverse nanocarriers from poly(ethylene glycol)-bl-poly(propylene sulfide) copolymers. These protocols will allow laboratories with a wide range of expertise and resources to easily and reproducibly fabricate advanced nanocarrier delivery systems for their applications. The design and construction of an automated instrument that employs a high-speed syringe pump to facilitate the flash nanoprecipitation process and to allow enhanced control over the homogeneity, size, morphology and loading of polymersome nanocarriers is described.

Nanomaterials provide versatile mechanisms of controlled therapeutic delivery for both basic science and translational applications, but their fabrication often requires expertise that is unavailable in most biomedical laboratories. Here, we present protocols for the scalable fabrication and therapeutic loading of diverse self-assembled nanocarriers using flash nanoprecipitation.

快速, 可伸缩的组装和负载的生物活性蛋白和免疫增强剂到不同的合成 Nanocarriers 通过闪光 Nanoprecipitation

Nanomaterials present a wide range of options to customize the controlled delivery of single and combined molecular payloads for therapeutic and imaging ...

Flash NanoPrecipitation for the Encapsulation of Hydrophobic and Hydrophilic Compounds in Polymeric Nanoparticles

The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can improve bioavailability and modify drug distribution within the body. For hydrophilic drugs like peptides or proteins, encapsulation within NPs can also provide protection from natural clearance mechanisms. There are few techniques for the production of polymeric NPs that are scalable. Flash NanoPrecipitation (FNP) is a process that uses engineered mixing geometries to produce NPs with narrow size distributions and tunable sizes between 30 and 400 nm. This protocol provides instructions on the laboratory-scale production of core-shell polymeric nanoparticles of a target size using FNP. The protocol can be implemented to encapsulate either hydrophilic or hydrophobic compounds with only minor modifications. The technique can be readily employed in the laboratory at milligram scale to screen formulations. Lead hits can directly be scaled up to gram- and kilogram-scale. As a continuous process, scale-up involves longer mixing process run time rather than translation to new process vessels. NPs produced by FNP are highly loaded with therapeutic, feature a dense stabilizing polymer brush, and have a size reproducibility of &#177; 6%.

Flash NanoPrecipitation (FNP) is a scalable approach to produce polymeric core-shell nanoparticles. Lab-scale formulations for the encapsulation of hydrophobic or hydrophilic therapeutics are described.

闪速纳米沉淀法包聚物纳米粒子中疏水亲水化合物的作用

The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can ...

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Self-assembly is a simple yet reliable method for constructing nanoscale drug delivery systems. Photoactivatable prodrugs enable controllable drug release from nanocarriers at target sites modulated by light irradiation. In this protocol, a facile method for fabricating photoactivatable prodrug-dye nanoparticles via molecular self-assembly is presented. The procedures for prodrug synthesis, nanoparticle fabrication, physical characterization of the nanoassembly, photocleavage demonstration, and in vitro cytotoxicity verification are described in detail. A photocleavable boron-dipyrromethene-chlorambucil (BC) prodrug was first synthesized. BC and a near-infrared dye, IR-783, at an optimized ratio, could self-assemble into nanoparticles (IR783/BC NPs). The synthesized nanoparticles had an average size of 87.22 nm and a surface charge of -29.8 mV. The nanoparticles disassembled upon light irradiation, which could be observed by transmission electronic microscopy. The photocleavage of BC was completed within 10 min, with a 22% recovery efficiency for chlorambucil. The nanoparticles displayed enhanced cytotoxicity under light irradiation at 530 nm compared with the non-irradiated nanoparticles and irradiated free BC prodrug. This protocol provides a reference&#160;for the construction and evaluation of photoresponsive drug delivery systems.

This protocol describes the fabrication and characterization of a photoresponsive prodrug-dye nanoassembly. The methodology for drug release from the nanoparticles by light-triggered disassembly, including the light irradiation setup, is explicitly described. The drugs released from the nanoparticles following light irradiation exhibited excellent anti-proliferation effects on human colorectal tumor cells.

前药染料纳米组件的简单制备和光活化

Self-assembly is a simple yet reliable method for constructing nanoscale drug delivery systems. Photoactivatable prodrugs enable controllable drug release ...

A'即插即用'的方法来创建水分散性Nanoassemblies包含两亲聚合物，有机染料和上变频纳米粒子

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