Cardiac-targeted FGF4 encapsulated nanoliposomes improve acute myocardial injury induced by ischemia-reperfusion and adriamycin in in vitro and in vivo models

Ischemia-reperfusion (IR) and adriamycin (also named doxorubicin, DOX)-induced acute myocardial injuries have a significant impact on health, causing serious economic and medical burdens. Therefore, we need to explore and identify drugs with potential therapeutic value for treating I/R- and DOX-induced myocardial injury. In the present study, we explored the therapeutic potential of FGF4 for I/R and DOX-induced myocardial injury. We found that FGF4 showed good improvement in acute cardiac injury. However, due to the short half-life of FGF4, we further prepared a myocardial-targeted FGF4-sustained release nanoliposome (named FGF4-NANO-IMTP). We investigated the effect of FGF4-NANO-IMTP on myocardial injury caused by I/R and DOX. <i>In vivo,</i> models of I/R and DOX-induced myocardial injury were established. Through a series of biochemical techniques (such as laser confocal scanning microscopy, electron microscopy, Western-blot, ELISA and gene knockdown techniques), we found that FGF4-NANO-IMTP can obviously alleviate myocardial injury caused by I/R and DOX by detecting a series of marker molecules. The mechanism study shows that FGF4-NANO-IMTP alleviated myocardial injury by inhibiting ferroptosis. In the cellular model, we analyzed the molecular mechanism by which FGF4 exhibits its biological functions. We found that FGF4 released from FGF4-NANO-IMTP binds to its FGFR1, which in turn activates the AMPK signaling pathway. AMPK-mediated downstream signaling pathways exert their inhibitory effect on myocardial ferroptosis. In summary, FGF4-NANO-IMTP can obviously improve I/R and DOX-induced myocardial injury. The current study lays an important research foundation for exploring the potential therapeutic effects of FGF4 targeting the heart.