From the journal:

RSC Chemical Biology

Reductively activated CPP–PROTAC nanocomplexes enhance target degradation via efficient cellular uptake

Maho Miyamoto,ab   Kosuke Saito,c   Hidetomo Yokoo*b  and  Yosuke Demizu ORCID logo *abd  

* Corresponding authors

a Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Yokohama 230-0045, Japan

b Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki 210-9501, Japan
E-mail: yokoo@nihs.go.jp, demizu@nihs.go.jp

c Division of Medicinal Safety Science, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki 210-9501, Japan

d Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

Abstract

We developed a nanoparticle based on a cell-penetrating peptide-PROTAC conjugate with a disulfide linker, MZ1-R9, and dextran sulfate, enhancing cellular uptake and BRD4 degradation. This delivery platform significantly improves PROTAC bioavailability and offers a promising strategy to overcome membrane permeability challenges for targeted protein degradation.

Graphical abstract: Reductively activated CPP–PROTAC nanocomplexes enhance target degradation via efficient cellular uptake

About
Cited by
Related
Download options Please wait...

Supplementary files

Article information

DOI
https://doi.org/10.1039/D5CB00196J
Article type
Communication
Submitted
30 Jul 2025
Accepted
22 Aug 2025
First published
25 Aug 2025
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2025, Advance Article

Permissions

Request permissions

Reductively activated CPP–PROTAC nanocomplexes enhance target degradation via efficient cellular uptake

M. Miyamoto, K. Saito, H. Yokoo and Y. Demizu, RSC Chem. Biol., 2025, Advance Article , DOI: 10.1039/D5CB00196J

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, 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 commercial 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