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

Dette arbejde blev støttet af prinsesse Margaret Hospital Foundation, National Science and Engineering Research Council of Canada, den canadiske Institute for Health Research, den canadiske Foundation for Innovation og Joey og Toby Tanenbaum / brasiliansk Ball Chair i Prostata Cancer Research, et tilskud fra SUNY Research Foundation og opstart støtte fra universitetet i Buffalo.

1.. Syntese af Pyropheophorbide-lipid <ol><li> Kombiner 200 mmol pyropheophorbide (fremstillet ud fra Spirulina Pacifica alger, som beskrevet tidligere... Zheng et al, Bioconj Chem, 2002, 13 -392) 4, 98,7 mg 16:00 lysophophatidylcholine (1-palmitoyl-2-hydroxy-sn-glycero -3-phosphocholin, Avanti Polar Lipids # 855675), 76,3 mg EDC, 48,7 mg DMAP (4 - (dimethylamino) pyridin) i 5 ml amylen stabiliseret chloroform til et forhold på 1:1:2:2 Pyro: Lipid: EDC : DMPA. </li><li> ...

<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>

I udviklingen af ​​drug delivery teknologier, er multifunktionelle nanopartikler i øjeblikket under brede undersøgelser for nøjagtig sporing af drug delivery køretøj samtidig opretholde en høj stof nyttelast. Porphyrin liposomer er blevet udviklet for bedre farmakokinetiske egenskaber og mere effektiv levering end direkte administration af porphyrin, men hindringer findes, herunder den begrænsede belastning mængden af porphyrin og hurtig omfordeling af porphyrin fra liposomer til plasmaproteiner 5,6.</s...

Porphysomes er nye multifunktionelle nanovesicles at vi for nylig udviklet som er i stand til multimodal billeddannelse og terapi 1.. De er dannet af selvsamlede porphyrin dobbeltlag og indeholder en ekstremt høj koncentration af porphyrin (over 83 000/porphysome partikel), som genererer store ekstinktionskoefficient og resulterer i en enestående struktur-afhængig fluorescens uden quenching. Porphysomes har gode in vivo farmakokinetiske og Biodistribution egenskaber: de udviser en halveringstid i blodet 12 timer efter systematisk indgivelse og passivt ophobes i xenotransplantattumorer med 7,5% ID / g efter 24 timer efter injektion 2. Deres unikke struktur og fysisk-kemiske egenskaber gør porphysome en god kandidat til multimodal billeddannelse og image-vejledt terapi. Først og fremmest porfyriner, porphysomes er uløseligt egnet til fluorescens billeddannelse af tumorer ved tumor opsummering 1.Derudover har hver porphyrin har en stabil site for chelaterende radioisotoper kan derfor porphysomes let mærkes med radioisotoper såsom 64Cu til PET-billeddannelse 3. Endvidere er den absorberede lysenergi spredes termisk under laserbestråling eksponering, når porphysome struktur er intakt, så porphysomes også udvise unikke fotoakustisk billedbehandling og PTT kapaciteter. Det er blevet vist, at 24 timer efter intravenøs injektion af porphysomes laser bestråling af porphysome akkumulerede tumorinduceret en hurtig temperaturstigning og stærk photothermal tumor ablation. Dette viste, at porphysomes er effektive photothermal smagsforstærkere med ekstinktionskoefficient så højt som guld nanopartikler (AuNPs) 1.. På den anden side, i sammenligning med andre uorganiske photothermal midler, herunder AuNPs, porphysomes viser en enestående fordel i biosikkerhed på grund af deres organiske natur. Porphysomes enzymatisk nedbrydelige og inducerer minimal akut toxicity i mus med intravenøse doser så høje som 1.000 mg / kg 1. Endvidere ligner liposomer, kunne store vandige kerne af porphysomes være passivt eller aktivt fyldt med terapeutisk eller billeddannende midler. De optiske egenskaber og biokompatibilitet porphysomes demonstrere den multimodale potentiale af organiske nanopartikler til BioPhotonic billeddannelse og terapi. I dette papir introducerer vi syntese metode pyropheophorbide-lipidkonjugater, fremstilling og karakterisering metode porphysomes anvender højtryks-ekstrudering. In vivo PTT på mus udføres samt for at demonstrere effektiviteten af porphysome-aktiverede PTT i tumoren behandling ved hjælp af en subkutan xenograft tumor model.

<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

Vi har for nylig udviklet porphysomes som reelt multifunktionelle nanovesicles. En fotosensibilisator pyropheophorbide α, blev konjugeret til et phospholipid og derefter selv-samlet til liposomlignende sfæriske vesikler. På grund af den ekstremt høje tæthed af porfyrin i porphyrin-lipiddobbeltlag porphysomes skabt store ekstinktionskoefficienter, struktur-afhængig fluorescens selv-quenching, og fremragende photothermal effekt. I vores formulering blev porphysomes syntetiseret under anvendelse af højt tryk ekstrudering, og viste en gennemsnitlig partikelstørrelse på omkring 120 nm. Fireogtyve timer efter intravenøs injektion af porphysomes, den lokale temperatur af tumoren steg fra 30 ° C til 62 ° C hurtigt ved en minutter eksponering på 750 mW (1,18 W / cm 2), 671 nm laser bestråling. Efter den fuldstændige termisk ablation af tumoren, eschars dannet og helbredte inden for 2 uger, mens kontrolgruppen tumorer fortsatte med at vokse og nåede alle de definerede end punkt inden for 3 uger. Disse data viser, hvordan porphysomes kan bruges som potent photothermal terapi (TOT) agenter.

Pyropheophorbide konjugeres til phospholipidet som en stabil lipid monomer (figur 1a) og konjugater selvsamle til dannelse porphysomes af membranen ekstrudering metode under anvendelse af en højtryks ekstruder. Det er normalt vanskeligt at ekstrudere porphysome-lipid-suspension i de første 3 cyklusser af ekstrudering med relativt langsom strømningshastighed. Efterhånden som flere ekstruderinger gentages strømningshastigheden af ​​ekstruderet opløsning øges gradvist, og trykket kan faldet en s...

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

Vi udviklede nye iboende multifunktionelle nanovesicles kaldet porphysomes, som har struktur-afhængige fluorescens selv-quenching og unikke photothermal egenskaber og fungerer dermed som potente photothermal terapi agenter. Vi formulerede porphysomes hjælp højtryk ekstrudering og undersøgte deres photothermal terapi effekt i en xenograft tumor model.

One Minute, Sub-One-Watt Photothermal Tumor Fjernelse Brug Porphysomes, Intrinsic Multifunktionel Nanovesicles

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

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