An antibody–supermolecule conjugate for cancer chemotherapy

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In this study, antibody–supermolecule conjugates, consisting of a tumor-specific antibody and acid-labile polyrotaxane containing methylated b-cyclodextrin (Me-PRX), were designed to achieve a tumor-specific delivery of Me-PRX. [1] Trastuzumab, a monoclonal antibody against HER2 expressed in various malignant tumors, was selected as a tumor-targeting antibody, and phenyl maleimide group-modified Me-PRX (Mal-Me-PRX) was conjugated to the cysteine residue of the reduced Trastuzumab to obtain a
Trastuzumab–Me-PRX conjugate (Tras-Me-PRX). The cellular association of Tras-Me-PRX to HER2-expressing tumor cells was remarkably greater than that of unmodified Me-PRX. Moreover, Tras-Me-PRX effectively reduced the viability of HER2-expressing tumor cells at a lower concentration compared to the unmodified Me-PRX. In conclusion, antibody–Me-PRX conjugates are regarded as a new class of antibody–drug conjugates that would contribute to the chemotherapy of cancers.

A Trastuzumab–Me-PRX conjugate was designed for the selective and efficient delivery of Me-PRX into HER2-positive tumor cells. The Trastuzumab–Me-PRX conjugate was prepared by Michael addition between the phenyl maleimide group-modified Me-PRX and the thiol groups of reduced antibodies. The cellular association of Tras-Me-PRX in HER2-overexpressing tumor cells was significantly higher than that of Me-PRX and IgG-Me-PRX, indicating that binding to HER2 plays an essential role in the cellular uptake of Tras-Me-PRX. The viability of HER2-positive tumor cells treated with Tras-Me-PRX decreased at a lower concentration compared to those treated with Me-PRX. These results suggest that the Tras-Me-PRX efficiently delivered the Me-PRX into the HER2-positive tumor cells and induced autophagic
cell death.

Nishida, K., Tamura, A., Kang, T. W., Masuda, H., & Yui, N. (2020). An antibody–supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes. Journal of Materials Chemistry B. doi:10.1039/d0tb00575d 

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