Effect of doxorubicin and SPEDOX-6 on human iPSC-derived cardiac spheroids comprised of cardiomyocytes, endothelial cells, and fibroblasts.
The chemotherapeutic doxorubicin (DOX) detrimentally impacts the heart during cancer treatment. This necessitates development of non-cardiotoxic delivery systems that retain DOX anticancer efficacy. We utilized human induced pluripotent stem cell-derived multi-lineage cardiac spheroids (hiPSC-CSs)  to compare the anticancer efficacy and reduced cardiotoxicity of single protein encapsulated doxorubicin (SPEDOX-6), to standard unformulated (UF) DOX using RNA-sequencing. The cardiac spheroids are comprised of hiPSC-derived cardiomyocytes (hiPSC-CMs), hiPSC-derived endothelial cells (ECs), and hiPSC-derived cardiac fibroblasts (CFs) at an 8:1:1 ratio. Overall design: Cardiac spheroid samples were treated with DMSO, unformulated doxorubicin at 5 micromolar, or SPEDOX-6 at 5 uM dox equivalent dose for 48 hours. RNA was then extracted using a QIAGEN RNA micro kit and submitted for bulk RNAsequencing.