# Regulatory T Cells and Nanomaterials: Dual Perspectives in Therapeutics and Immunomodulation

## TL;DR

This paper explores how nanomaterials can be used to control regulatory T cells for immune-related therapies in autoimmunity, transplantation, and cancer.

## Contribution

The paper introduces how nanomaterials can be engineered to selectively modulate regulatory T cells for therapeutic purposes.

## Key findings

- Nanoparticles can be designed to expand or stabilize regulatory T cells for tolerogenic therapy.
- The same nanomaterials can be used to inhibit tumor-associated regulatory T cells to enhance antitumor immunity.
- Unintended immunological effects of nanoparticles, such as Treg induction or immunosuppression, are also discussed.

## Abstract

Regulatory T cells (Tregs) orchestrate immune tolerance, protecting against autoimmunity and promoting transplant tolerance, yet they can also facilitate tumor immune evasion. Advances in nanotechnology now permit high‐precision manipulation of Treg biology. Tailored polymeric, lipid‐based, inorganic, and biomimetic nanoparticles can be engineered to deliver antigens, cytokines, small‐molecule drugs, antibodies, or nucleic acids that selectively expand or stabilize Tregs for tolerogenic therapy; the same design principles can be inverted to inhibit or deplete intratumoral Tregs, thereby restoring effective antitumor immunity. Beyond intentional therapies, the review also explores unintended immunological consequences of nanoparticles, such as inadvertent induction of Tregs or broader immunosuppressive responses, and how Tregs can conversely limit the efficacy of nanoparticle‐based vaccines or cancer nanotherapies. Outstanding challenges related to targeting efficiency, safety, manufacturability, and combinatorial therapeutic strategies are outlined, and prospective avenues for future investigation are highlighted. Collectively, emerging data position Treg‐focused nanomedicine as a versatile and clinically relevant toolkit for restoring or unleashing immunity across autoimmunity, transplantation, and oncology.

Tregs control immune tolerance but can also enable tumor escape. Nanomaterials can now expand or stabilize Tregs to treat autoimmunity and support transplantation or conversely disrupt tumor Tregs to boost antitumor immunity. We also discuss unintended Treg modulation by nanoparticles, safety and manufacturing challenges, and future translational opportunities.© 2026 WILEY‐VCH GmbH