# Polyarginine Peptide R11–Actin Interaction Induces a Domino Effect on Cytoskeleton Remodeling to Suppress Bladder Cancer Metastasis

## TL;DR

A polyarginine peptide called R11 disrupts actin in bladder cancer cells, preventing their spread to the lungs by altering the cytoskeleton.

## Contribution

R11 is a novel, bladder tumor-targeting peptide that modulates actin dynamics to suppress metastasis through a domino effect on the cytoskeleton.

## Key findings

- R11 interacts with actin to weaken the actin–plectin–vimentin/integrin β4 axis, impairing cellular motility.
- Multivalent R11 assemblies enhance actin binding and amplify anti-metastatic effects in bladder cancer.
- R11-based materials offer a promising therapeutic platform for cytoskeleton-dependent cancers.

## Abstract

Cytoskeletal remodeling, particularly actin dynamics, is a central driver of tumor metastasis. However, actin-targeting agents have faced major translational barriers due to poor specificity and the absence of defined druggable sites. Here, we report a bladder tumor-targeting polyarginine peptide, R11, as a precision modulator of actin dynamics capable of disrupting the cytoskeletal architecture of bladder cancer (BCa) to suppress its lung metastasis potently and persistently. R11 directly interacts with actin, weakening the actin–plectin–vimentin/integrin β4 axis and initiating a cascade of cytoskeletal disorganization that ultimately impairs cellular motility and metastatic potential. Remarkably, nanoscale multivalent assemblies of R11 amplify these effects through enhanced multivalent binding to actin. This study unveils a new strategy for cytoskeleton-targeted intervention through peptide-based precision materials, highlighting R11 assemblies as a promising therapeutic platform for the treatment of metastatic BCa and potentially other cytoskeleton-dependent malignancies.