Opinion: Gavage Administration of MXene as a Route-Specific Alternative to Intravenous Injection into the Bloodstream of Laboratory Animals for Reducing Systemic Nanotoxicity Risks in Immunosuppression and Post-Transplantation Models with Bile Acid Modification.

Intravenous injection of engineered material dispersions into the bloodstream of laboratory animals has been a popular method for in vivo immunosuppression. It is also one of the primary approaches for delivering immunosuppressive and anti-inflammatory drugs within the early stages of donor cell/organ transplantation. Due to their systemic interaction with blood circulation and immune cells, the administration is reported to act effectively in suppressing host immune responses. Recent studies on immunomodulatory nanomaterials, including MXenes, have reported their potential for immunosuppression and post-transplantation applications. In particular, MXene nanosheets and quantum dots of specific composition/form possess immunosuppressive properties that prevent stem/progenitor cell and cardiac transplant rejection, including the treatment of allograft vasculopathy, an accelerated form of atherosclerosis in organ recipients. Despite these promising in vivo findings, concerns regarding long-term blood nanotoxicity or particle accumulation in circulatory organs, such as the heart, liver, kidneys, and lungs, as well as the associated risks of metabolic changes and other potential adverse biological pathways, remain challenging for clinical applications. This opinion perspective proposes the rational concept of gavage administration of bile acid-modified MXenes, which may alleviate these risks while retaining their intrinsic immunosuppressive roles. It also presents novel density functional theory calculations for cholic acid surface modification to enhance MXenes' immune-suppressive properties and synergistically interact with gut beneficial microbiomes for smart interaction, bringing this nanobiotechnology closer to real-world scenarios.