Liposomal nanoparticles containing adenosine triphosphate targeted by heart-specific peptide ligands as antidotes for aluminum phosphide poisoning in isolated rat cardiomyocyte cell line.

Abstract

Aluminum phosphide (ALP) poisoning remains a critical challenge because of the limited number of treatment options. ALP disrupts the electron transport chain, causing ATP depletion, oxidative stress, and cytotoxicity. This study developed ischemic myocardium-targeting peptide (IMTP)-conjugated ATP-loaded liposomes (ATP-L) to mitigate ALP-induced cardiotoxicity. ATP-L was prepared via thin-film hydration and freeze-thaw methods, followed by peptide conjugation via maleimide-PEG₂₀₀₀-DSPE. Liposome characterization revealed average sizes of 134.8 nm (DLS) and 113 nm (TEM), zeta potential of +11.33 mV, PDI of 0.17, and ATP encapsulation efficiency of 41 %. In this study, the rat cardiomyocyte cell line (H₉C₂) was used. In H₉C₂ cells, ALP exhibited dose-dependent toxicity, whereas ATP, non-targeted ATP-loaded liposomes (NT-ATP-L), and ATP-L showed no cytotoxicity. Co-treatment with ATP, NT-ATP-L, and ATP-L via ALP (18.27 μg/ml) for 3 h significantly reduced the levels of oxidative stress markers, restoring the cellular redox balance. These findings highlight ATP-L as a promising antioxidant nanotherapy for treating ALP poisoning. ATP-L combats ALP-induced cardiotoxicity by restoring ATP and reducing oxidative damage. The use of IMTP ensures precise targeting to ischemic cardiac tissues, potentially improving efficacy and minimizing off-target effects. This strategy offers a novel approach to managing ALP toxicity. Further studies are needed to validate the in vivo results and optimize the formulation for clinical use. Overall, ATP-L represents a significant advancement in targeted nanomedicine for toxicological emergencies.