Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to tar...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-020-0573-0 |
| _version_ | 1798026364932063232 |
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| author | Pablo Lara Sujey Palma-Florez Edison Salas-Huenuleo Iva Polakovicova Simón Guerrero Lorena Lobos-Gonzalez America Campos Luis Muñoz Carla Jorquera-Cordero Manuel Varas-Godoy Jorge Cancino Eloísa Arias Jaime Villegas Luis J. Cruz Fernando Albericio Eyleen Araya Alejandro H. Corvalan Andrew F. G. Quest Marcelo J. Kogan |
| author_facet | Pablo Lara Sujey Palma-Florez Edison Salas-Huenuleo Iva Polakovicova Simón Guerrero Lorena Lobos-Gonzalez America Campos Luis Muñoz Carla Jorquera-Cordero Manuel Varas-Godoy Jorge Cancino Eloísa Arias Jaime Villegas Luis J. Cruz Fernando Albericio Eyleen Araya Alejandro H. Corvalan Andrew F. G. Quest Marcelo J. Kogan |
| author_sort | Pablo Lara |
| collection | DOAJ |
| description | Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs. |
| first_indexed | 2024-04-11T18:35:26Z |
| format | Article |
| id | doaj.art-5b82f674541a454f83c81bb4f433339c |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:35:26Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5b82f674541a454f83c81bb4f433339c2022-12-22T04:09:19ZengBMCJournal of Nanobiotechnology1477-31552020-01-0118111710.1186/s12951-020-0573-0Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumorsPablo Lara0Sujey Palma-Florez1Edison Salas-Huenuleo2Iva Polakovicova3Simón Guerrero4Lorena Lobos-Gonzalez5America Campos6Luis Muñoz7Carla Jorquera-Cordero8Manuel Varas-Godoy9Jorge Cancino10Eloísa Arias11Jaime Villegas12Luis J. Cruz13Fernando Albericio14Eyleen Araya15Alejandro H. Corvalan16Andrew F. G. Quest17Marcelo J. Kogan18Departamento de Química Farmacológica Y Toxicológica, Universidad de ChileDepartamento de Química Farmacológica Y Toxicológica, Universidad de ChileDepartamento de Química Farmacológica Y Toxicológica, Universidad de ChileAdvanced Center for Chronic Diseases (ACCDiS)Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), University of ChileAdvanced Center for Chronic Diseases (ACCDiS)Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), University of ChileLaboratorio de Análisis Por Activación Neutrónica, Comisión Chilena de Energía NuclearLaboratory of Cellular Communication, Program of Cell and Molecular Biology, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), University of ChileCentro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San SebastiánCentro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San SebastiánCentro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San SebastiánEscuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andrés BelloTranslational Nanobiomaterials and Imaging (TNI) Group, Radiology Department, Leiden University Medical CenterCIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, and Department of Organic Chemistry, University of BarcelonaDepartamento de Ciencias Quimicas, Universidad Andres BelloAdvanced Center for Chronic Diseases (ACCDiS)Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), University of ChileDepartamento de Química Farmacológica Y Toxicológica, Universidad de ChileAbstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.https://doi.org/10.1186/s12951-020-0573-0Extracellular vesiclesExosomesGold nanoparticlesMetastasisTrackingTargeting |
| spellingShingle | Pablo Lara Sujey Palma-Florez Edison Salas-Huenuleo Iva Polakovicova Simón Guerrero Lorena Lobos-Gonzalez America Campos Luis Muñoz Carla Jorquera-Cordero Manuel Varas-Godoy Jorge Cancino Eloísa Arias Jaime Villegas Luis J. Cruz Fernando Albericio Eyleen Araya Alejandro H. Corvalan Andrew F. G. Quest Marcelo J. Kogan Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors Journal of Nanobiotechnology Extracellular vesicles Exosomes Gold nanoparticles Metastasis Tracking Targeting |
| title | Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| title_full | Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| title_fullStr | Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| title_full_unstemmed | Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| title_short | Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| title_sort | gold nanoparticle based double labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors |
| topic | Extracellular vesicles Exosomes Gold nanoparticles Metastasis Tracking Targeting |
| url | https://doi.org/10.1186/s12951-020-0573-0 |
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