'Golden' exosomes as delivery vehicles to target tumors and overcome intratumoral barriers: tracking in a model for head and neck cancer

• Published in: Biomaterials science 2021-03, Vol.9 (6), p.213-2114
• Main Authors: Cohen, Oded, Betzer, Oshra, Elmaliach-Pnini, Noy, Motiei, Menachem, Sadan, Tamar, Cohen-Berkman, Moran, Dagan, Or, Popovtzer, Aron, Yosepovich, Ady, Barhom, Hana, Michaeli, Shulamit, Popovtzer, Rachela
• Format: Article
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d0bm01735c

Exosomes are promising vectors for anti-tumor therapy, due to their biocompatibility, low immunogenicity, and innate ability to interact with target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome biodistribution, tumor targeting and accumulation, and the ability to overcome tumor barriers that limit the penetration of various nano-carriers and drugs. Here, we examined these parameters in exosomes derived from mesenchymal stem cells (MSC- exo ) and from the A431 squamous cell carcinoma line (A431- exo ), which both have potential use in cancer therapy. Using our novel technique combining gold nanoparticle (GNP) labeling of exosomes and non-invasive computed tomography imaging (CT), we longitudinally and quantitatively tracked the two intravenously-injected exosome types in A431 tumor-bearing mice. CT imaging up to 48 h and subsequent ex vivo analysis revealed tumor homing abilities of both exosome types, yet there was significantly higher tumor accumulation of MSC- exo as compared to A431- exo . Moreover, MSC- exo demonstrated the ability to penetrate the tumor and distribute throughout its bulk, while non-encapsulated GNPs remained concentrated at the tumor periphery. Histological analysis showed penetration of MSC- exo not only into the tumor tissue, but also into tumor cell cytoplasm. While the proportion of biodistribution between organs at 48 h was similar for both exosome types, more rapid clearance was indicated for A431- exo . Thus, our findings demonstrate an effect of exosome type on tumor targeting abilities and biodistribution, and suggest that MSC- exo may have superior abilities for tumor-targeted therapy. Exosomes are promising vectors for anti-tumor therapy. In this research, both in-vivo CT tracking and ex-vivo measurements revealed better tumor targeting, accumulation and penetration of MSC-derived exosomes as compared to A431-derived exosomes.