Name: one minute, sub-one-watt photothermal tumor ablation using porphysomes, intrinsic multifunctional nanovesicles
Uploaded: 2013-09-17T19:30:00
Description: Watch this Scientific Journal Video about One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles at JoVE.com

这项工作是由玛嘉烈医院基金会，美国国家科学和加拿大，加拿大卫生研究院，创新的加拿大基础工程研究理事会，以及乔伊和托比的Tanenbaum /巴西球椅在前列腺癌研究，支持一个授予纽约州立大学研究基金会和大学水牛城分校的启动支持。

1。焦脱脂质的合成<ol><li>结合200毫摩尔焦脱（如前所述螺旋藻茵藻类制备;。郑等人 ，Bioconj化学，2002年，13 -392）4，98.7毫克十六时lysophophatidylcholine（1 -棕榈酰-2 -羟基-sn-甘油基-3 - 磷酸胆碱，阿凡提极性脂质＃855675），76.3毫克的EDC，48.7毫克的DMAP（4 - （二甲氨基）吡啶）的5ml戊烯稳定的氯仿为1:1:2:2烟火的比率：脂质：EDC ：DMPA的。 </li><li>在室温下搅拌反应?...

<ol>
	<li>Lovell, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Porphysome+nanovesicles+generated+by+porphyrin+bilayers+for+use+as+multimodal+biophotonic+contrast+agents.">Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents.</a> Nat. Mater. 10, 324-332 (2011).</li><li>Lovell, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enzymatic+regioselection+for+the+synthesis+and+biodegradation+of+porphysome+nanovesicles.">Enzymatic regioselection for the synthesis and biodegradation of porphysome nanovesicles.</a> Angew Chem Int Ed Engl. 51, 2429-2433 (2012).</li><li>Liu, T. W., MacDonald, T. D., Shi, J., Wilson, B. C., Zheng, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intrinsically+Copper-64-Labeled+Organic+Nanoparticles+as+Radiotracers.">Intrinsically Copper-64-Labeled Organic Nanoparticles as Radiotracers.</a> Angewandte Chemie. , (2012).</li><li>Zheng, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-density+lipoprotein+reconstituted+by+pyropheophorbide+cholesteryl+oleate+as+target-specific+photosensitizer.">Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer.</a> Bioconjug Chem. 13, 392-396 (2002).</li><li>Chen, B., Pogue, B. W., Hasan, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liposomal+delivery+of+photosensitising+agents.">Liposomal delivery of photosensitising agents.</a> Expert Opin Drug Deliv. 2, 477-487 (2005).</li><li>Jin, C. S., Zheng, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liposomal+nanostructures+for+photosensitizer+delivery.">Liposomal nanostructures for photosensitizer delivery.</a> Lasers Surg Med. 43, 734-748 (2011).</li><li>Olson, F., Hunt, C. A., Szoka, F. C., Vail, W. J., Papahadjopoulos, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+liposomes+of+defined+size+distribution+by+extrusion+through+polycarbonate+membranes.">Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes.</a> Biochim Biophys Acta. 557, 9-23 (1979).</li><li>Berger, N., Sachse, A., Bender, J., Schubert, R., Brandl, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Filter+extrusion+of+liposomes+using+different+devices:+comparison+of+liposome+size,+encapsulation+efficiency,+and+process+characteristics.">Filter extrusion of liposomes using different devices: comparison of liposome size, encapsulation efficiency, and process characteristics.</a> Int J Pharm. 223, 55-68 (2001).</li><li>Jesorka, A., Orwar, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liposomes:+technologies+and+analytical+applications.">Liposomes: technologies and analytical applications.</a> Annu Rev Anal Chem (Palo Alto Calif). 1, 801-832 (2008).</li><li>Lapinski, M. M., Castro-Forero, A., Greiner, A. J., Ofoli, R. Y., Blanchard, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+liposomes+formed+by+sonication+and+extrusion:+rotational+and+translational+diffusion+of+an+embedded+chromophore.">Comparison of liposomes formed by sonication and extrusion: rotational and translational diffusion of an embedded chromophore.</a> Langmuir. 23, 11677-11683 (2007).</li><li>Liu, D., Huang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Size+Homogeneity+of+a+Liposome+Preparation+is+Crucial+for+Liposome+Biodistribution+In+Vivo.">Size Homogeneity of a Liposome Preparation is Crucial for Liposome Biodistribution In Vivo.</a> Journal of Liposome Research. 2, 57-66 (1992).</li><li>Zhang, Y., Lovell, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Porphyrins+as+Theranostic+Agents+from+Prehistoric+to+Modern+Times.">Porphyrins as Theranostic Agents from Prehistoric to Modern Times.</a> Theranostics. 2, 905-915 (2012).</li></ol>

中的药物递送技术的发展，多官能纳米粒子是目前正在广泛研究的药物递送载体的精确跟踪，同时保持高的药物的有效载荷。卟啉-脂质体已经被开发用于更好的药代动力学特性和更有效地提供比卟啉的直接施用，但存在的障碍，包括卟啉的受限负载量和卟啉的快速再分配从脂质体与血浆蛋白5,6。相对于传统的脂质体递送系统，其中自由卟啉被插入到脂质体中的任一核心或脂质双层，焦脱?...

Porphysomes是我们最近开发的新型多功能纳米囊泡，它们能够多模式成像和治疗1。它们是由自组装卟啉双分子层形成，并含有极高密度卟啉（超过83，000/porphysome颗粒），从而产生较大的消光系数，并导致独特的结构依赖的荧光自猝灭。 Porphysomes具有良好的体内药物动力学和生物分布性质：它们显示出12小时的血中半衰期以下系统的管理，并被动地积聚在异种移植肿瘤有7.5％ID / g的在24小时后注射2。 其独特的结构和理化性质做出porphysome一个很好的候选人，多模式成像和图像引导治疗。首先，含有卟啉，porphysomes本质上是适合的肿瘤时的肿瘤积累1荧光成像。此外，每个卟啉具有稳定的网站螯合放射性同位素，因此，porphysomes可以很容易地用放射性同位素标记如64Cu用于PET成像3。此外，所吸收的光的能量下激光照射曝光的热消散时porphysome结构是完整的，所以porphysomes也表现出独特的光声成像和PTT功能。它已经显示，24小时静脉注射porphysomes后，本porphysome积累的肿瘤的激光照射引起的温度的急剧上升和强的光热肿瘤消融。这表明porphysomes是有效率的光热增强与消光系数高达金纳米粒子（纳米金）1。在另一方面，与其它无机光热剂，包括纳米金相比，porphysomes显示生物安全的突出优势，由于其有机性。 Porphysomes是可生物降解酶和诱发急性最小toxicitÝ小鼠静脉内剂量高达1000毫克/千克1。此外，类似于脂质体，porphysomes的大型水核可以是被动或主动加载的治疗或成像剂。的光学特性和porphysomes的生物相容性证明有机纳米粒子的生物光子成像和治疗的多峰电位。 在本文中，我们介绍的焦脱-脂质共轭物的合成方法，在制造和使用高压挤出porphysomes的表征方法。 体内 PTT对小鼠中进行，以及证明porphysome启用PTT在肿瘤的效率治疗采用皮下移植瘤模型。

<table border="1">
	<tbody>
		<tr>
			<td>Name of Equipment</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments (optional)</td>
		</tr>
		<tr>
			<td>Rotary evaporator</td>
			<td>Thermo-Savant</td>
			<td>SPD131DDA</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Votex</td>
			<td>Scientific Industries</td>
			<td>SI-0236</td>
			<td>Model number: G560</td>
		</tr>
		<tr>
			<td>High pressure extruder</td>
			<td>LIPEX, Northern Lipids Inc.</td>
			<td>T.001</td>
			<td>10 ml Thermobarrel Extruder</td>
		</tr>
		<tr>
			<td>Heated bath circulators (Thermostatted circulator)</td>
			<td>Thermo SCIENTIFIC</td>
			<td>SC100-S5P</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Polycarbonate filters</td>
			<td>Avanti Polar Lipids</td>
			<td>610005</td>
			<td>Pore size 100 nm, and membrane diameter 19 mm</td>
		</tr>
		<tr>
			<td>Zetasizer</td>
			<td>Malvern Instruments</td>
			<td>ZS90</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>UV/Visible Spectrophototmeter</td>
			<td>Varian Australia</td>
			<td>Cary 50 Bio UV/ Visible Spectrophotometer</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Spectrofluorometer</td>
			<td>HORIBA Scientific</td>
			<td>FluoroMax-4</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Transmission Electron Microscopy (TEM)</td>
			<td>Hitachi</td>
			<td>H-7000</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Cell culture incubator</td>
			<td>SANYO</td>
			<td>MCO-18AIC</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Powermeter</td>
			<td>Thorlabs</td>
			<td>PM100D</td>
			<td>with sensor S142C</td>
		</tr>
		<tr>
			<td>671nm Laser</td>
			<td>LaserGlow Technologies</td>
			<td>LRS-0671_PFN-02000-05</td>
			<td>S/N:10097270</td>
		</tr>
		<tr>
			<td>Infrared Thermometer</td>
			<td>Mikroshot, LUMASENSE Technologies</td>
			<td>9102409</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Laser protective eye goggles</td>
			<td>LaserGlow Technologies</td>
			<td>AGF6602XX</td>
			<td>Optical Density: 1.5+ at 630-700 nm</td>
		</tr>
	</tbody>
</table>

one minute, sub-one-watt photothermal tumor ablation using porphysomes, intrinsic multifunctional nanovesicles

我们最近开发porphysomes为本质的多功能纳米囊泡。光敏剂，焦脱α，缀合到磷脂，然后自组装到脂质体样球形囊泡。由于卟啉的卟啉 - 脂质双分子层的密度非常高，porphysomes产生大的消光系数，结构依赖性的荧光自猝灭，以及卓越的光热功效。在我们的制剂，合成porphysomes采用高压挤出，和大约120纳米显示的平均粒度。二十四小时后静脉注射porphysomes的，肿瘤的局部温度从30°C时为750毫瓦（1.18瓦/厘米2），671 nm激光照射1分钟风险迅速上升至62℃。随着肿瘤的完全消融，焦痂2周​​内形成和愈合，而在对照组的肿瘤继续生长，并全部达到定义的连接3周内三维点。这些数据表明porphysomes如何可以用作有效的光热治疗（PTT）剂。

焦脱缀合到磷脂作为稳定脂质单体（ 图1a）和缀合物自我装配由膜挤出法使用高压挤出来形成porphysomes。它通常是难以在挤出过程中的前3个循环用相对慢的流速挤出porphysome - 脂质悬浮液。随着越来越多的挤压重复，挤压溶液的流速逐渐增大，并且压力可以在需要时略有下降。 Porphysome大小，浓度和淬火效率是在挤出后右侧的纳米粒子来表征的三个重要特性。 Porphysomes具有高均匀粒度?...

Watch this Scientific Journal Video about One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles at JoVE.com

One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles

我们开发了新的内在的多功能纳米囊泡称为porphysomes，它具有结构依赖性荧光自猝灭和独特的光热特性，从而起到有效的光热治疗剂。我们制定了利用高压挤压porphysomes并研究了它们的光热治疗的疗效在异种移植瘤模型。

一分钟，小一瓦光热消融肿瘤使用Porphysomes，内在多功能纳米囊泡

We recently developed porphysomes as intrinsically multifunctional nanovesicles. A photosensitizer, pyropheophorbide &alpha;, was conjugated to a ...

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