De novo design strategies of nanomedicines for antigen-specific immune tolerance modulation

Background A failure of immune tolerance underlies autoimmune disorders, leading to abnormal responses against the body's own antigens and subsequent tissue damage. The number of people affected by autoimmune diseases is on the rise. Current treatment strategies primarily rely on nonspecific immunosuppression, while this approach is effective in alleviating symptoms, it fails to restore immune homeostasis and is often associated with significant adverse effects. Against this background, tolerance induction targeting specific antigens has come to represent a notably compelling new direction, aiming to selectively reprogram autoreactive immune cells while preserving protective immunity, with growing attention focused on leveraging advances in materials science and computational design to enable the de novo engineering of nanomedicines for precise and programmable immunomodulation. Technology This review offers a thorough summary concerning the immunological principles that underpin tolerance directed at specific antigens, highlights the advantages of nanomedicine in immunotherapy, and elucidates the key design requirements for nanoplatforms used to induce tolerance, as well as the multifaceted enabling role of artificial intelligence in this field. Results By integrating and comparing preclinical studies on various nanomaterial systems, this review systematically summarizes the key mechanisms by which these nanoplatforms induce immune tolerance. Incorporating these mechanisms into precisely engineered nanocarriers holds promise for achieving a lasting and disease-specific restoration of immune balance. These insights offer a fresh, from-scratch design framework for realizing antigen-specific immune tolerance via the transformative approach of nanomedicine, thereby revealing its extensive potential for treating autoimmune disorders as well as other diseases.