Light-Activated Gold-Selenium Core-Shell Nanocomposites with NIR-II Photoacoustic Imaging Performances for Heart-Targeted Repair.
Yu SunPu ZhangYuqing LiYajun HouChenyang YinZekun WangZiyu LiaoXiaoyan FuMan LiCundong FanDongdong SunLiang ChengPublished in: ACS nano (2022)
Mitochondrial dysfunction and oxidative damage represent important pathological mechanisms of myocardial ischemia-reperfusion injury (MI/RI). Searching for potential antioxidant agents to attenuate MI/RI is of great significance in clinic. Herein, gold-selenium core-shell nanostructures (AS-I/S NCs) with good near-infrared (NIR)-II photoacoustic imaging were designed for MI/RI treatment. The AS-I/S NCs after ischemic myocardium-targeted peptide (IMTP) and mitochondrial-targeted antioxidant peptide SS31 modification achieved cardiomyocytes-targeted cellular uptake and enhanced antioxidant ability and significantly inhibited oxygen-glucose deprivation-recovery (OGD/R)-induced cardiotoxicity of H9c2 cells by inhibiting the depletion of mitochondrial membrane potential (MMP) and restoring ATP synthase activity. Furthermore, the AS-I/S NCs after SS31 modification achieved mitochondria-targeted inhibition of reactive oxygen species (ROS) and subsequently attenuated oxidative damage in OGD/R-treated H9c2 cells by inhibition of apoptosis and oxidative damage, regulation of MAPKs and PI3K/AKT pathways. The in vivo AS-I/S NCs administration dramatically improved myocardial functions and angiogenesis and inhibited myocardial fibrosis through inhibiting myocardial apoptosis and oxidative damage in MI/RI of rats. Importantly, the AS-I/S NCs showed good safety and biocompatibility in vivo . Therefore, our findings validated the rational design that mitochondria-targeted selenium-gold nanocomposites could attenuate MI/RI of rats by inhibiting ROS-mediated oxidative damage and regulating MAPKs and PI3K/AKT pathways, which could be a potential therapy for the MI/RI treatment.
Keyphrases
- cell cycle arrest
- pi k akt
- cell death
- signaling pathway
- oxidative stress
- reactive oxygen species
- induced apoptosis
- cancer therapy
- ischemia reperfusion injury
- left ventricular
- cell proliferation
- fluorescence imaging
- dna damage
- high resolution
- diabetic rats
- endoplasmic reticulum stress
- anti inflammatory
- photodynamic therapy
- drug delivery
- endothelial cells
- high glucose
- risk assessment
- heart failure
- replacement therapy
- silver nanoparticles
- human health
- skeletal muscle
- carbon nanotubes
- insulin resistance
- blood glucose
- atrial fibrillation
- climate change
- drug induced
- endoplasmic reticulum