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A Magnetic Separation-Assisted High-Speed Homogenization Method for Large-Scale Production of Endosome-Derived Vesicles

Extracellular vesicles (EVs) have attracted significant attention in physiological and pathological research, disease diagnosis, and treatment; however, ...

Chinese Academy of Sciences

Tianjin University

Parathyroid gland (PG) injury is the most common complication of thyroidectomy owing to the lack of approaches for surgeons to effectively distinguish PGs from surrounding thyroid glands (TGs) in the operation room. Herein, we report the development of biodegradable iron oxide nanoparticles (IONPs) as a promising contrast agent candidate for intraoperative PG visualization. We elucidated that locally administrated dark-colored IONPs readily diffuse in TGs but cannot infiltrate tissue-dense PGs, yielding a distinguishable contrast enhancement between PGs and TGs by naked eye observation. We performed unbiased and quantitative in vivo screenings to optimize particle size and concentration of IONPs for PG/TG contrast enhancement. Moreover, in vivo applications of IONPs via the local administration route demonstrate no adverse toxicities and can be biodegraded in the thyroid microenvironment within 3 months. To our knowledge, these promising findings provide the first in vivo evidence that IONPs can serve as a safe, biodegradable, and effective contrast agent candidate for improving PG visualization in thyroidectomy.

Biodegradable iron oxide nanoparticles for intraoperative parathyroid gland imaging in thyroidectomy.

Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells . Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.

Shili Yao

Hangzhou Institute of Medicine (HIM)

Chinese Academy of Sciences

A Magnetic Separation-Assisted High-Speed Homogenization Method for Large-Scale Production of Endosome-Derived Vesicles

Shili Yao

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Chinese Academy of Sciences

A Magnetic Separation-Assisted High-Speed Homogenization Method for Large-Scale Production of Endosome-Derived Vesicles

Hangzhou Institute of Medicine (HIM)