Key result
Doxorubicin-functionalized gold nanoparticles fail to prevent cardiotoxicity, worsening LVEF vs. free doxorubicin.
Why the study?
Gold nanoparticles have been explored to enhance antitumor efficacy and minimize doxorubicin cardiotoxicity, but their impacts on cardiac function and oxidative stress remain inadequately understood.
Does doxorubicin functionalized with gold nanoparticles reduce cardiotoxicity compared to free doxorubicin in an in vivo rat model?
Does doxorubicin functionalized with gold nanoparticles reduce cardiotoxicity compared to free doxorubicin in an in vivo rat model?
Doxorubicin incorporated into gold nanoparticles fails to protect against cardiotoxicity and instead worsens myocardial oxidative stress and cardiac dysfunction compared to free doxorubicin.
Answers are grounded in this paper and cite their sources.
Gold nanoparticle-doxorubicin conjugates worsen cardiotoxicity in rats; leaves open whether alternative nanocarrier designs merit further preclinical testing.
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.
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Cîmpan et al. (2024) studied Doxorubicin-induced cardiotoxicity (n=40). Doxorubicin-functionalized gold nanoparticles (DOX Au-NPs) vs. Free doxorubicin (10 mg/kg), citrate Au-NPs, and saline (control) was evaluated on Ejection fraction (LVEF) (p=0.011). Doxorubicin-functionalized gold nanoparticles failed to mitigate cardiotoxicity, significantly reducing ejection fraction (p=0.011) and exacerbating oxidative stress compared to free doxorubicin.
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