Targeting breast cancer exosomes with nucleic aptamers: Innovative tools for early diagnosis and therapy

Exosomes are emerging as promising target for early diagnosis and therapy in different oncological conditions including breast cancer (BC). However, the development of tools able to easily and specifically target cancer cell-derived exosomes still represent a fundamental issue that is required to realize their clinical utility. Nucleic-acid aptamers are a promising class of structured single stranded oligonucleotides that serve as high affinity ligands of disease-associated proteins. Given their high potential in diagnosis and therapy, we addressed the development of aptamers specific for BC-derived exosomes. To this end, we developed a novel SELEX strategy by using exosomes purified from primary BC cells as positive selection target. By such a strategy we isolated nuclease resistant RNA aptamers able to specifically discriminate BC-derived exosomes from those produced by normal cells. The best sequences were optimized identifying short molecules (about 30-35 mer) that was characterized as tools for exosome detection. Further, we demonstrated that the developed aptamers inhibited exosome cellular uptake antagonizing cancer exosome-induced cell migration. By proteomic approach we identified possible targets that we are characterizing. Our results underline the great potential of isolated aptamers as tools for the development of innovative strategies for BC early diagnosis and therapy.