Advances in nanomaterial-based delivery systems for inducing transplantation tolerance

Organ transplantation is the primary therapeutic approach for patients with end-stage organ failure. However, challenges such as transplant rejection, the toxic side effects of long-term systemic immunosuppression, and substantial economic burdens remain pressing issues in clinical practice. The goal of inducing donor-specific transplantation tolerance is considered the most effective strategy to address these problems. Conventional tolerance-inducing strategies, including hematopoietic chimerism establishment, costimulatory signal blockade, and regulatory cell therapy, are often hampered by key limitations such as myeloablative toxicity, resistance from memory T cells, high costs associated with ex vivo cell expansion, and poor in vivo stability. This review summarizes the types and properties of nanomaterials used to induce transplantation tolerance, systematically discusses their payload categories and immunoregulatory mechanisms, and delineates key delivery strategies and in vivo mechanisms. Furthermore, it analyzes current challenges and bottlenecks faced by nanodelivery systems. Finally, future perspectives on optimizing and translating these systems into clinical applications are proposed, providing valuable insights for developing safe, precise, and efficient strategies for transplantation tolerance induction.