Smuggling gold nanoparticles across cell types – a new role for exosomes in gene silencing

• Published in: Nanomedicine Vol. 13; no. 4; pp. 1389 - 1398
• Main Authors: Roma-Rodrigues, Catarina, Pereira, Francisca, Alves de Matos, António P, Fernandes, Marta, Baptista, Pedro V, Fernandes, Alexandra R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2017
• Subjects: Breast cancer; Cell Line, Tumor; Cell–cell communication; Exosomes; Exosomes - genetics; Gene Silencing; Gold - chemistry; Gold nanoparticles; Humans; Internal Medicine; MicroRNAs - genetics; Nanoconjugates - chemistry; Oligonucleotides, Antisense - chemistry; rab GTP-Binding Proteins - genetics; rab27 GTP-Binding Proteins; Exosomes; Breast Cancer; Gold Nanoparticles; Gene Silencing; Cell–cell communication; Gene silencing; Breast cancer; Gold nanoparticles
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2017.01.013

Abstract Once released to the extracellular space, exosomes enable the transfer of proteins, lipids and RNA between different cells, being able to modulate the recipient cells' phenotypes. Members of the Rab small GTP-binding protein family, such as RAB27A , are responsible for the coordination of several steps in vesicle trafficking, including budding, mobility, docking and fusion. The use of gold nanoparticles (AuNPs) for gene silencing is considered a cutting-edge technology. Here, AuNPs were functionalized with thiolated oligonucleotides anti- RAB27A (AuNP@PEG@anti- RAB27A ) for selective silencing of the gene with a consequent decrease of exosomes´ release by MCF-7 and MDA-MB-453 cells. Furthermore, communication between tumor and normal cells was observed both in terms of alterations in c-Myc gene expression and transportation of the AuNPs, mediating gene silencing in secondary cells.