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.

Autor: Lara P; Departamento de Química Farmacológica Y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494, Santiago, Chile.; 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 Chile, Av. Independencia 1027, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile., Palma-Florez S; Departamento de Química Farmacológica Y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile., Salas-Huenuleo E; Departamento de Química Farmacológica Y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile., Polakovicova I; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile.; Laboratory of Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Santiago, Chile., Guerrero S; 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 Chile, Av. Independencia 1027, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile.; Instituto de investigación Interdisciplinar en Ciencias biomédicas, Universidad SEK (I3CBSEK). Facultad Ciencias de La Salud, Fernando Manterola 0789, Santiago, Chile., Lobos-Gonzalez L; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile.; Centro de Medicina Regenerativa, Facultad de Medicina-Clinica Alemana, Universidad Del Desarrollo, Avenida las condes 12438, lo Barnechea, Santiago, Chile., Campos A; 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 Chile, Av. Independencia 1027, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile., Muñoz L; Laboratorio de Análisis Por Activación Neutrónica, Comisión Chilena de Energía Nuclear, Nueva Bilbao, 12501, Santiago, Chile., Jorquera-Cordero C; 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 Chile, Av. Independencia 1027, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile., Varas-Godoy M; Centro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San Sebastián, Lota 2465, Santiago, Chile., Cancino J; Centro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San Sebastián, Lota 2465, Santiago, Chile., Arias E; Centro de Biología Celular Y Biomedicina (CEBICEM), Facultad de Medicina Y Ciencia, Universidad San Sebastián, Lota 2465, Santiago, Chile., Villegas J; Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Republica 440, Santiago, Chile., Cruz LJ; Translational Nanobiomaterials and Imaging (TNI) Group, Radiology Department, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands., Albericio F; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, and Department of Organic Chemistry, University of Barcelona, 08028, Barcelona, Spain., Araya E; Departamento de Ciencias Quimicas, Universidad Andres Bello, Republica 275, 8370146, Santiago, Chile., Corvalan AH; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile.; Laboratory of Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Santiago, Chile., Quest AFG; 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 Chile, Av. Independencia 1027, Santiago, Chile. aquest@med.uchile.cl.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile. aquest@med.uchile.cl., Kogan MJ; Departamento de Química Farmacológica Y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494, Santiago, Chile. mkogan@ciq.uchile.cl.; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Santiago, Chile. mkogan@ciq.uchile.cl.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2020 Jan 23; Vol. 18 (1), pp. 20. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1186/s12951-020-0573-0
Abstrakt: 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.
Databáze: MEDLINE
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