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Mitochondrial ncRNA targeting induces cell cycle arrest and tumor growth inhibition of MDA-MB-231 breast cancer cells through reduction of key cell cycle progression factors

2019 , Christopher Fitzpatrick , Maximiliano F. Bendek , Macarena Briones , Nicole Farfán , Valeria A. Silva , Gino Nardocci , Martín Montecino , Anne Boland , Jean-François Deleuze , Jaime Villegas , Claudio Villota , Verónica Silva , LOBOS GONZALEZ, LORENA DE LOURDES , Vincenzo Borgna , Eric Barrey , Luis O. Burzio , Verónica A. Burzio

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Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

2017 , Vincenzo Borgna , Jaime Villegas , Verónica A. Burzio , Sebastián Belmar , Mariela Araya , Emanuel Jeldes , LOBOS GONZALEZ, LORENA DE LOURDES , Verónica Silva , Claudio Villota , Luciana Oliveira-Cruz , Constanza Lopez , Teresa Socias , Octavio Castillo , Luis O. Burzio

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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.