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

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.