1. Nano-Encapsulation of Coenzyme Q10 in Secondary and Tertiary Nano-Emulsions for Enhanced Cardioprotection and Hepatoprotection in Human Cardiomyocytes and Hepatocytes During Exposure to Anthracyclines and Trastuzumab
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Quagliariello V, Vecchione R, De Capua A, Lagreca E, Iaffaioli RV, Botti G, Netti PA, and Maurea N
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cardio-oncology ,nano-medicine ,coenzyme q10 ,doxorubicin ,trastuzumab ,inflammation ,Medicine (General) ,R5-920 - Abstract
Vincenzo Quagliariello,1,* Raffaele Vecchione,2,* Alberta De Capua,2 Elena Lagreca,2 Rosario Vincenzo Iaffaioli,3 Gerardo Botti,4 Paolo A Netti,2 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, Italia; 2Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Naples, Italy; 3Multidisciplinary Studies in Oncology and Mediterranean Diet, Piazza Nicola Amore, Naples, Italy; 4Scientific Direction, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, Italia*These authors contributed equally to this workCorrespondence: Vincenzo QuagliarielloDivision of Cardiology, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, ItaliaTel +390815903349Email quagliariello.enzo@gmail.comIntroduction: CoenzymeQ10 (CoQ10) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ10 is based on its very low oral bioavailability and instability that limit dramatically its effects as a cardioprotective agent. Herein, we loaded CoQ10 in high bioavailable nano-emulsions (NEs) coated with chitosan or chitosan and hyaluronic acid in order to improve its performance.Methods: We tested cardioprotective and hepatoprotective effects of CoQ10-loaded nano-carriers against Doxorubicin and Trastuzumab toxicities in cardiomyocytes and liver cells through analysis of cell viability, lipid peroxidation, expression of leukotrienes, p65/NF-kB and pro-inflammatory cytokines involved in anticancer-induced cardio and hepatotoxicity.Results: Nano-carriers showed high stability and loading ability and increased cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. We observed that these effects are mediated by the inhibition of lipid peroxidation and reduction of the inflammation. CoQ10-loaded nano-emulsions showed also strong anti-inflammatory effects reducing leukotriene B4 and p65/NF-κB expression and Interleukin 1β and 6 production during anticancer treatments.Discussion: Anthracyclines and Human epidermal growth factor receptor (HER2) inhibitors have shown significant anticancer effects in clinical practice but their use is characterized by cardiotoxicity and hepatotoxicity. Nano-carriers loaded with CoQ10 showed cardio and hepatoprotective properties mediated by reduction of oxidative damages and pro-inflammatory mediators. These results set the stage for preclinical studies of cardio and hepatoprotection in HER2+ breast cancer-bearing mice treated with Doxorubicin and Trastuzumab.Keywords: cardio-oncology, nano-medicine, Coenzyme Q10, doxorubicin, trastuzumab, inflammation
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- 2020