LOBOS GONZALEZ, LORENA DE LOURDES
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LOBOS GONZALEZ, LORENA DE LOURDES
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llobos@udd.cl
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28767817600

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Biomimetic quantum dot-labeled B16F10 murine melanoma cells as a tool to monitor early steps of lung metastasis by in vivo imaging

2018 , Victor Manuel Díaz-García , Simón Guerrero , Natalia Díaz-Valdivia , LOBOS GONZALEZ, LORENA DE LOURDES , Marcelo Kogan , José Pérez-Donoso , Andrew F.G. Quest

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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

2020 , Pablo Lara , Sujey Palma-Florez , Edison Salas-Huenuleo , Iva Polakovicova , Simón Guerrero , LOBOS GONZALEZ, LORENA DE LOURDES , 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

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.

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Gold nanoparticles as tracking devices to shed light on the role of caveolin-1 in early stages of melanoma metastasis

2018 , Simón Guerrero , Victor Manuel Díaz-García , Pamela Contreras-Orellana , Pablo Lara , Sujey Palma , Fanny Guzman , LOBOS GONZALEZ, LORENA DE LOURDES , Areli Cárdenas , Ximena Rojas-Silva , Luis Muñoz , Lisette Leyton , Marcelo J Kogan , Andrew FG Quest

Aim: To track early events during lung metastasis, we labeled cells expressing (B16F10CAV1) or lacking CAV1 (B16F10mock) with gold nanoparticles conjugated to the peptide TAT (AuNPs-PEG-TAT). Methods: B16F10 expressing or lacking CAV1 were labeled with AuNPs-PEG-TAT. The physicochemical properties and cytotoxicity of these nanoparticles, as well as their effects on migration and invasiveness of B16F10 cells in vitro were evaluated. Ex vivo lung distribution of the labeled cells after tail vein injection into C57BL/6 mice was examined. Results: AuNPs-PEG-TAT did not affect B16F10 viability, migration and invasiveness. The metastatic and tumorigenic capability of the labeled B16F10 was also not modified in comparison to unlabeled B16F10 cells. CAV1 expression favored the retention of B16F10 cells in the lungs of mice 2 h post injection, suggesting CAV1 promoted adherence to endothelial cells and transendothelial migration. Conclusions: We developed a protocol to label B16F10 cells with AuNPs-PEG-TAT that permits subsequent tracking of cells in mice. CAV1 overexpression was found to increase retention and transendothelial migration of B16F10 cells in the lung.

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