Dual-Modal Nanoscavenger for Detoxification of Organophosphorus Compounds

Abstract

Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte–liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood–brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.

Biomimetic ZIF-8 Nanoparticles: A Novel Approach for Biomimetic Drug Delivery Systems

“…The outcomes of the investigation evinced that the developed decontaminant evinced substantial preventive detoxification efficacy against methyl paraoxon (MP) poisoning and demonstrated the remarkable ability to successfully transgress the blood-brain barrier. 30 Furthermore, an additional study endeavored to enhance the therapeutic precision of cervical cancer treatment through the manipulation of the red blood cell membrane via cyclic RGD (cRGD) modification and the subsequent encapsulation of DOX within ZIF-8 nanoparticles. 32 This pioneering drug delivery system, boasting an impressive drug loading capacity of 49%, effectively harnessed the enhanced permeability and retention (EPR) effect to promote the preferential accumulation of nanoparticles within tumor tissues.…”

Understanding the Air‐Exposure Degradation Chemistry of the Sacrificial Cathode Additive Li5FeO4 for Li‐Ion Batteries

“…Unfortunately, understanding the underlying reaction mechanism between LFO and air is quite limited. In spite of some early success, [ 12 ] it is still rather challenging to effectively suppress the degradation process of LFOs exposed to air. Therefore, it is essential to study the LFO‐air interface chemistry to develop a feasible strategy for practically implementing cathode prelithiation materials for Li‐ion batteries.…”

Tuning the Envelope Structure of Enzyme Nanoreactors for In Vivo Detoxification of Organophosphates

“…The creation of nanoreactors for trapping toxicants involves the complete sealing of enzyme molecules inside an nR body, and must ensure long-term circulation in the body to trap and neutralize toxicants present in the bloodstream and may be slowly released from cellular and organ depot sites, e.g., OP molecules may accumulate in fat from where they are subsequently slowly released into the bloodstream again [2,20,21]. Attempts to use OP-reacting enzymes and their encapsulated forms for stoichiometric or catalytic inactivation of OPs have been undertaken for more than 20 years and have led to very effective formulations [22,23] and novel nanoscavenger devices for OP detoxification [24,25]. However, important issues, such as the operational stability of nano-formulations and fate in organisms after administration (degradation, elimination, and immunogenicity) for the safe use of non-human enzymes have not been completely solved [26][27][28].…”