Issue 41, 2022

An assembly-inducing PDC enabling the efficient nuclear delivery of nucleic acid for cancer stem-like cell suppression

Abstract

Nucleic acid therapy is attracting great attention in diverse clinical translations because of its therapeutic advantages. As a renowned oligonucleotide therapeutical candidate in the clinical stage, AS1411 has shown outstanding tumor suppressing effects; however, its efficient delivery to the cell nucleus is critical for its anticancer effect. Herein, we identified a multifunctional peptide drug conjugate (PDC) as a safe and efficient carrier to achieve the nuclear delivery of AS1411. This PDC consists of the cell penetration peptide RW9, an HDAC inhibitor warhead (peptide C-terminus), and 5-FU (peptide N-terminus), which can coassemble with AS1411 to form nanospheres. The PDC efficiently delivered AS1411 to the nucleus of several types of cancer cells. Moreover, it reversed the stemness of a cancer stem-like cell line. Significantly, due to the assembly-induced accumulation enhancement and retention, a safe single agent concentration of PDC showed unexpected synergy with AS1411 to augment the cancer cell suppression efficiency, exemplified by the downregulation of the stemness-related proteins and the upregulation of apoptosis-related proteins. Therefore, our work presents a powerful strategy for the nuclear delivery of nucleic acid drugs by leveraging cancer-suppressing PDC as assembly inducers, which provides a powerful combination regimen in treating cancer stem-like cells.

Graphical abstract: An assembly-inducing PDC enabling the efficient nuclear delivery of nucleic acid for cancer stem-like cell suppression

Supplementary files

Article information

Article type
Paper
Submitted
17 avr. 2022
Accepted
08 sept. 2022
First published
06 oct. 2022

Nanoscale, 2022,14, 15384-15392

An assembly-inducing PDC enabling the efficient nuclear delivery of nucleic acid for cancer stem-like cell suppression

D. Wang, Y. Tian, Y. Zhang, X. Sun, Y. Wu, R. Liu, F. Zeng, J. Du and K. Hu, Nanoscale, 2022, 14, 15384 DOI: 10.1039/D2NR02118H

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