Precise engineering of iron oxide nanoparticle-encapsulated protein hydrogel: Implications for cardiac toxicity and ultrasound contrast agents

Abstract

In the present study, we developed and assessed novel injectable hydrogel matrices combined with nanoparticles and secretome biomolecules to reduce Doxorubicin (DOX)- induced cytotoxicity in human stem cell-derived cardiomyocytes. A Fe2O3 nanoparticle-loaded biocompatible silk sericin (MSS) nanocomposite form was fabricated and used as an injectable carrier for secretome for in vivo cardiomyocyte metabolism. Biological analyses revealed that the secretome-encapsulated Fe3O2-Silk sericin (Sec@MSS) hydrogel markedly reduced acridine orange/ethidium bromide (AOEB) dual staining in cardiomyocytes, revealing significantly induced apoptosis. Furthermore, we evaluated the mitochondrial membrane potential for DOX and Sec@MSS hydrogel, and demonstrated apoptosis of the cardiomyocytes in the DOX-alone and Sec@MSS groups. However, the cardiotoxicity of Sec@MSS sericin was much lower than that in the DOX group. The acoustic behaviors of the functionalized Sec@MSS were examined. The results indicate that Sec@MSS hydrogel might serve as an effective treatment agent in cardiac diseases in the future.