Dulf Patricia Lorena, Coadă Camelia Alexandra, Florea Adrian, Moldovan Remus, Baldea Ioana, Dulf Daniel Vasile, Blendea Dan, David Luminita, Moldovan Bianca, Morosan Valentina Ioana, Macavei Sergiu, Filip Gabriela Adriana
Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Molecular Sciences, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Nanomaterials (Basel). 2024 Oct 14;14(20):1647. doi: 10.3390/nano14201647.
Gold nanoparticles (Au-NPs) have been explored as potential vectors for enhancing the antitumor efficacy of doxorubicin (DOX) while minimizing its cardiotoxic effects. However, the impacts of DOX Au-NPs on cardiac function and oxidative stress remain inadequately understood. This study aimed to explore the effects of DOX Au-NPs in comparison to free DOX, focusing on oxidative stress markers, inflammation, ultrastructural changes, and cardiac function. Male rats were divided into the following four groups: control, citrate Au-NPs, DOX, and DOX Au-NPs. Cardiac function was assessed using echocardiography, and oxidative stress was evaluated through Nrf2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, and the GSH/GSSG ratio. The ultrastructure of cardiac tissue was assessed by transmission electron microscopy (TEM). Rats treated with DOX Au-NPs exhibited significant cardiac dysfunction, as indicated by a reduction in fractional shortening and ejection fraction. Oxidative stress markers, including elevated MDA levels and a reduced GSH/GSSG ratio, were significantly worse in the DOX Au-NP group. SOD levels decreased, indicating compromised antioxidant defenses. Citrate Au-NPs also caused some alterations in cardiac function and ultrastructure but without other molecular alterations. DOX Au-NPs failed to mitigate cardiotoxicity, instead exacerbating oxidative stress and cardiac dysfunction. DOX Au-NPs possess cardiotoxic effects, necessitating further investigation into alternative nanoparticle formulations or therapeutic combinations to ensure both efficacy and safety in cancer treatment.
金纳米颗粒（Au-NPs）已被探索作为增强阿霉素（DOX）抗肿瘤疗效同时将其心脏毒性降至最低的潜在载体。然而，DOX Au-NPs对心脏功能和氧化应激的影响仍未得到充分了解。本研究旨在探讨DOX Au-NPs与游离DOX相比的作用，重点关注氧化应激标志物、炎症、超微结构变化和心脏功能。雄性大鼠被分为以下四组：对照组、柠檬酸盐Au-NPs组、DOX组和DOX Au-NPs组。使用超声心动图评估心脏功能，并通过Nrf2、丙二醛（MDA）和超氧化物歧化酶（SOD）水平以及谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值评估氧化应激。通过透射电子显微镜（TEM）评估心脏组织的超微结构。DOX Au-NPs处理的大鼠表现出明显的心脏功能障碍，表现为缩短分数和射血分数降低。DOX Au-NP组的氧化应激标志物，包括MDA水平升高和GSH/GSSG比值降低，明显更严重。SOD水平降低，表明抗氧化防御受损。柠檬酸盐Au-NPs也引起了心脏功能和超微结构的一些改变，但没有其他分子改变。DOX Au-NPs未能减轻心脏毒性，反而加剧了氧化应激和心脏功能障碍。DOX Au-NPs具有心脏毒性，需要进一步研究替代纳米颗粒制剂或治疗组合，以确保癌症治疗中的疗效和安全性。
