Development of ROS-responsive liposomes toward targeted drug delivery

Elevated levels of reactive oxygen species (ROS), which are key mediators in different pathophysiological conditions, provide a unique opportunity for achieving targeted drug delivery. As such, ROS-responsive liposomes that undergo variable structural changes have emerged as promising tools for drug delivery purposes. These approaches show strong prospects for enhancing the selectivity of delivery to diseased cells through nanoparticle activation by aberrant ROS concentrations. This review describes elegant strategies for engineering ROS-responsive liposomes through lipid switch oxidation. These platforms exhibit improvements, including ROS-triggered release of encapsulated cargo, detachment of medicinal agents through prodrug strategies, programmed activation of cellular delivery, and photodynamic therapies. We describe how lipid switch design features can be leveraged to achieve these varying applications. ROS-responsive liposomes provide an adaptable approach for targeted therapy in environments associated with higher oxidative stress. We discuss how the attributes of each platform position these systems for overcoming practical issues, including stability, scalability, and clinical efficacy, as well as strategies for maximizing properties through continued innovation. In general, ROS-responsive liposome stability must be carefully tuned to be sufficiently stable to survive circulation but become activated within a window of ROS concentration that differentiates between diseased and healthy cells.