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

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

Resultado de la investigación: Article

Resumen

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.

Idioma originalEnglish
Número de artículo20
PublicaciónJournal of Nanobiotechnology
Volumen18
N.º1
DOI
EstadoPublished - 23 ene 2020

Huella dactilar

Gold
Nanoparticles
Labeling
Tumors
Melanoma
Lung
Neoplasms
Fluorescence
Cells
Proteins
Tropism
Imaging techniques
Neutron activation analysis
Macrophages
Polydispersity
Surface charge
Fluorescent Dyes
Optical microscopy
Tomography
Extracellular Vesicles

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

Citar esto

Lara, Pablo ; Palma-Florez, Sujey ; Salas-Huenuleo, Edison ; Polakovicova, Iva ; Guerrero, Simón ; Lobos-Gonzalez, Lorena ; Campos, America ; Muñoz, Luis ; Jorquera-Cordero, Carla ; Varas-Godoy, Manuel ; Cancino, Jorge ; Arias, Eloísa ; Villegas, Jaime ; Cruz, Luis J. ; Albericio, Fernando ; Araya, Eyleen ; Corvalan, Alejandro H. ; Quest, Andrew F.G. ; Kogan, Marcelo J. / 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. En: Journal of Nanobiotechnology. 2020 ; Vol. 18, N.º 1.
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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",
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.",
keywords = "Drug delivery, Exosomes, Extracellular vesicles, Gold nanoparticles, Metastasis, Targeting, Tracking",
author = "Pablo Lara and Sujey Palma-Florez and Edison Salas-Huenuleo and Iva Polakovicova and Sim{\'o}n Guerrero and Lorena Lobos-Gonzalez and America Campos and Luis Mu{\~n}oz and Carla Jorquera-Cordero and Manuel Varas-Godoy and Jorge Cancino and Elo{\'i}sa Arias and Jaime Villegas and Cruz, {Luis J.} and Fernando Albericio and Eyleen Araya and Corvalan, {Alejandro H.} and Quest, {Andrew F.G.} and Kogan, {Marcelo J.}",
year = "2020",
month = "1",
day = "23",
doi = "10.1186/s12951-020-0573-0",
language = "English",
volume = "18",
journal = "Journal of Nanobiotechnology",
issn = "1477-3155",
publisher = "BioMed Central",
number = "1",

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Lara, P, Palma-Florez, S, Salas-Huenuleo, E, Polakovicova, I, Guerrero, S, Lobos-Gonzalez, L, Campos, A, Muñoz, L, Jorquera-Cordero, C, Varas-Godoy, M, Cancino, J, Arias, E, Villegas, J, Cruz, LJ, Albericio, F, Araya, E, Corvalan, AH, Quest, AFG & Kogan, MJ 2020, '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, vol. 18, n.º 1, 20. https://doi.org/10.1186/s12951-020-0573-0

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. / Lara, Pablo; Palma-Florez, Sujey; Salas-Huenuleo, Edison; Polakovicova, Iva; Guerrero, Simón; Lobos-Gonzalez, Lorena; Campos, America; Muñoz, Luis; Jorquera-Cordero, Carla; Varas-Godoy, Manuel; Cancino, Jorge; Arias, Eloísa; Villegas, Jaime; Cruz, Luis J.; Albericio, Fernando; Araya, Eyleen; Corvalan, Alejandro H.; Quest, Andrew F.G.; Kogan, Marcelo J.

En: Journal of Nanobiotechnology, Vol. 18, N.º 1, 20, 23.01.2020.

Resultado de la investigación: Article

TY - JOUR

T1 - 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

AU - Lara, Pablo

AU - Palma-Florez, Sujey

AU - Salas-Huenuleo, Edison

AU - Polakovicova, Iva

AU - Guerrero, Simón

AU - Lobos-Gonzalez, Lorena

AU - Campos, America

AU - Muñoz, Luis

AU - Jorquera-Cordero, Carla

AU - Varas-Godoy, Manuel

AU - Cancino, Jorge

AU - Arias, Eloísa

AU - Villegas, Jaime

AU - Cruz, Luis J.

AU - Albericio, Fernando

AU - Araya, Eyleen

AU - Corvalan, Alejandro H.

AU - Quest, Andrew F.G.

AU - Kogan, Marcelo J.

PY - 2020/1/23

Y1 - 2020/1/23

N2 - 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.

AB - 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.

KW - Drug delivery

KW - Exosomes

KW - Extracellular vesicles

KW - Gold nanoparticles

KW - Metastasis

KW - Targeting

KW - Tracking

UR - http://www.scopus.com/inward/record.url?scp=85078240294&partnerID=8YFLogxK

U2 - 10.1186/s12951-020-0573-0

DO - 10.1186/s12951-020-0573-0

M3 - Article

C2 - 31973696

AN - SCOPUS:85078240294

VL - 18

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

SN - 1477-3155

IS - 1

M1 - 20

ER -