Isolation of Cancer-Derived Exosomes Using a Variety of Magnetic Nanostructures: From Fe3O4 Nanoparticles to Ni Nanowires

使用各种磁性纳米结构分离癌症衍生的外泌体:从 Fe3O4 纳米粒子到 Ni 纳米线

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作者:Zohreh Nemati, Mohammad Reza Zamani Kouhpanji, Fang Zhou, Raja Das, Kelly Makielski, Joseph Um, Manh-Huong Phan, Alicia Muela, Ma Luisa Fdez-Gubieda, Rhonda R Franklin, Bethanie J H Stadler, Jaime F Modiano, Javier Alonso6

Abstract

Isolating and analyzing tumor-derived exosomes (TEX) can provide important information about the state of a tumor, facilitating early diagnosis and prognosis. Since current isolation methods are mostly laborious and expensive, we propose herein a fast and cost-effective method based on a magnetic nanoplatform to isolate TEX. In this work, we have tested our method using three magnetic nanostructures: (i) Ni magnetic nanowires (MNWs) (1500 × 40 nm), (ii) Fe3O4 nanorods (NRs) (41 × 7 nm), and (iii) Fe3O4 cube-octahedral magnetosomes (MGs) (45 nm) obtained from magnetotactic bacteria. The magnetic response of these nanostructures has been characterized, and we have followed their internalization inside canine osteosarcoma OSCA-8 cells. An overall depiction has been obtained using a combination of Fluorescence and Scanning Electron Microscopies. In addition, Transmission Electron Microscopy images have shown that the nanostructures, with different signs of degradation, ended up being incorporated in endosomal compartments inside the cells. Small intra-endosomal vesicles that could be precursors for TEX have also been identified. Finally, TEX have been isolated using our magnetic isolation method and analyzed with a Nanoparticle tracking analyzer (NanoSight). We observed that the amount and purity of TEX isolated magnetically with MNWs was higher than with NRs and MGs, and they were close to the results obtained using conventional non-magnetic isolation methods.

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