A fast-acting brain-targeted nano-delivery system with ultra-simple structure for brain emergency poisoning rescue

Treatment for acute brain conditions remains a major challenge owing to the unavailability of antidotes, especially for organophosphorus compounds, exposure to which leads to rapid death. Despite recent advances in brain-targeted nano delivery systems (BTNDS), the traditional ones which have been developed will likely not lead to the quick release of an antidote, which is essential to counteract fast neurotoxic effects. Herein, we present a BTNDS using thermosensitive liposomes, without the need for functionalization, to obtain a platform for brain-targeted delivery, which has a simple structure and thus can be easily synthesized and scaled-up. The brain-targeting effect of BTNDS was amplified by phospholipase A2 (PLA2), an inflammatory biomarker. The combination of PLA2 and BTNDS significantly improved brain targeting, leading to an excellent emergency rescue effect - 83- and 4.8-fold better cerebral AChE reactivation response and survival time, respectively. These findings provide a promising strategy to generate a facile, druggable, and effective BTNDS.