Lead halide perovskites (LHPs) are outstanding candidates for next-generation optoelectronic materials, with considerable prospects of use and commercial value. However, knowledge about their toxicity is scarce, which may limit their commercialization. Here, for the first time, we studied the cardiotoxicity and molecular mechanisms of representative CsPbBr3 nanoparticles in LHPs. After their intranasal administration to Institute of Cancer Research (ICR) mice, using advanced synchrotron radiation, mass spectrometry, and ultrasound imaging, we revealed that CsPbBr3 nanoparticles can severely affect cardiac systolic function by accumulating in the myocardial tissue. RNA sequencing and Western blotting demonstrated that CsPbBr3 nanoparticles induced excessive oxidative stress in cardiomyocytes, thereby provoking endoplasmic reticulum stress, disturbing calcium homeostasis, and ultimately leading to apoptosis. Our findings highlight the cardiotoxic effects of LHPs and provide crucial toxicological data for the product.
Keywords: CsPbBr3; biodistribution; biotransformation; cardiotoxicity; damage mechanism.