Redox-responsive LNPs for therapeutics delivery

Redox-responsive lipid nanoparticles (LNPs) are emerging as a powerful platform for precision nanomedicine by exploiting disease-associated redox imbalances, such as elevated glutathione and reactive oxygen species, to trigger controlled cargo release and structural activation. This strategy is of great importance for developing gene-based therapeutics, where efficient cytosolic delivery is essential. In addition to nucleic acids, redox-responsive LNPs have also been explored in delivering small molecules, proteins, and theranostic agents, broadening their potential in both cancer and non-cancer diseases. This review summarizes the biological basis of redox responsiveness, key design principles for responsive chemical structures, and major advances in payload delivery and targeting capability of LNP carriers. Moreover, some major bottlenecks, including redox heterogeneity, stability, responsiveness trade-offs, and translational complexity, are critically discussed. Future directions are also highlighted, particularly for organ-selective delivery, multifunctional theranostics, and clinically translatable LNP-based medicines.