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
Journal of Nanobiotechnology
ISSN
1477-3155
Date Issued
2020
Author(s)
Pablo Lara
Sujey Palma-Florez
Edison Salas-Huenuleo
Iva Polakovicova
Simón Guerrero
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
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85078240294
WoS ID
WOS:000513161700001
DOI
URL
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
Cite this document
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, L. J., Albericio, F., Araya, E., Corvalan, A. H., Quest, A. F. G., & Kogan, M. J. (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, 18(1), 20. https://doi.org/10.1186/s12951-020-0573-0
Subjects
extracellular vesicles

; 

exosomes

; 

gold nanoparticles

; 

metastasis

; 

tracking

; 

targeting

; 

drug delivery

; 

metastasis

; 

adenocarcinoma

; 

animals

; 

antineoplastic agents

; 

cell line, tumor

; 

cell membrane permeability

; 

colonic neoplasms

; 

extracellular vesicles

; 

fluorescent dyes

; 

gold

; 

humans

; 

lung

; 

lung neoplasms

; 

melanoma

; 

melanoma, experimental

; 

metal nanoparticles

; 

mice

; 

mice, inbred c57bl

; 

optical imaging

; 

surface properties

; 

tissue distribution

; 

biological organs

; 

cells

; 

controlled drug delivery

; 

cytology

; 

diseases

; 

drug delivery

; 

fiber optic sensors

; 

fluorescence imaging

; 

gold nanoparticles

; 

mammals

; 

metal nanoparticles

; 

neutron activation analysis

; 

pathology

; 

plasmonic nanoparticles

; 

plasmonics

; 

proteins

; 

surface discharges

; 

tumors

; 

fluorescent dye

; 

gold nanoparticle

; 

antineoplastic agent

; 

gold

; 

metal nanoparticle

; 

deep tissue imaging

; 

exosomes

; 

extracellular

; 

fluorescence analysis

; 

histological analysis

; 

metastasis

; 

surface functionalization

; 

targeting

; 

animal cell

; 

animal experiment

; 

animal model

; 

animal tissue

; 

article

; 

bioaccumulation

; 

cancer cell

; 

cell interaction

; 

cell migration

; 

cell specificity

; 

cell structure

; 

cell transport

; 

cellular distribution

; 

colon adenocarcinoma

; 

computer assisted tomography

; 

controlled study

; 

dispersity

; 

endosome

; 

exosome

; 

fluorescence analysis

; 

histopathology

; 

in vitro study

; 

internalization

; 

kidney

; 

liver

; 

lung

; 

lung metastasis

; 

macrophage

; 

melanoma

; 

microscopy

; 

mouse

; 

neutron activation analysis

; 

nonhuman

; 

particle size

; 

quantitative analysis

; 

spleen

; 

surface charge

; 

tropism

; 

adenocarcinoma

; 

animal

; 

c57bl mouse

; 

cell membrane permeability

; 

chemistry

; 

colon tumor

; 

diagnostic imaging

; 

exosome

; 

experimental melanoma

; 

fluorescence imaging

; 

human

; 

lung tumor

; 

melanoma

; 

metabolism

; 

surface property

; 

tissue distribution

; 

tumor cell line

; 

targeted drug delivery