MXenes at the Immune Interface: A Perspective on Influence of Physicochemical Design in Immunomodulation

Abstract MXenes are a recently discovered family of two-dimensional (2D) transition metal-based nanomaterials, known for their compositional diversity, exceptional tunability, structural versatility, and surface functionality. Beyond their well-established application in energy storage, MXenes have attracted growing interest for their promising role in regenerative biomedicine, particularly in antimicrobial and immune engineering applications. Recent studies, including contributions from our group, demonstrate that MXenes exhibit unique interactions with immune cells and associated immunosuppressive functions. Notably, MXene nanosheets and derived quantum dots can be tailored to modulate key immunosuppressive mechanisms, including the enhancement of regulatory T-cells (Tregs), reduction of proinflammatory cytokines, macrophages modulation and autophagy induction. These findings position MXenes as potential next-generation platform for immunomodulatory therapy, either as standalone agents or in combination with existing immunosuppressants. In this perspective, we systematically examine how physiochemical parameters including size, dimension, morphology, surface chemistry, and functionalization govern their interactions with innate and adaptive system. We highlight recent advances in MXene-mediated immunomodulation, paving a roadmap for further investigations, by identifying key knowledge gaps and translational challenges. We further outline future research directions necessary to bridge the divide between experimental studies, artificial intelligence (AI)-driven optimization/predictive approaches, and clinical applications of MXene-based immunotherapies.