Issue 31, 2020

An antibody–supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes

Abstract

We previously found that acid-labile polyrotaxane containing methylated β-cyclodextrin (Me-PRX) induces endoplasmic reticulum (ER) stress-related autophagy and autophagic cell death. Me-PRX-induced autophagic cell death occurs even in apoptosis-resistant cells; tumor-targeted Me-PRX delivery could thus be an effective cancer treatment approach. In this study, antibody–supermolecule conjugates, consisting of a tumor-specific antibody and Me-PRX, were designed to achieve a tumor-specific delivery of Me-PRX. 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.

Graphical abstract: An antibody–supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
03 мар 2020
Accepted
09 июн 2020
First published
23 июн 2020

J. Mater. Chem. B, 2020,8, 6975-6987

An antibody–supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes

K. Nishida, A. Tamura, T. W. Kang, H. Masuda and N. Yui, J. Mater. Chem. B, 2020, 8, 6975 DOI: 10.1039/D0TB00575D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements