Porous magnetic Silica nanoparticles loaded with sulforaphane mitigate myocardial infarction injury through upregulating HSP70

Abstract

Myocardial infarction (MI) is a common cardiovascular disease that induces an extensive sterile inflammation in the early stage, but usually seriously endangers human health. The modulation of cardiac inflammation may improve the outcome of post MI. Unfortunately, due to therapeutic drugs’ side effects and the cardiac coronary artery occlusion, currently MI drugs always can hardly fulfill the myocardial ischemia environment and clinical requirements. Considering the myocardial protective effect and low toxicity of sulforaphane (SFN), SFN was adopted for the treatment of MI. However, it is still difficult for the targeted accumulation of SFN in the infarcted area. Herein, porous magnetic silica nanoparticles (PMSNs) were synthesized and loaded with sulforaphane (SFN) to improve the efficiency by targeted delivery to the infarcted area in MI mice. PMSNs loaded with SFN (PMSNs+SFN) decreased the pro-inflammatory cytokines, thus improving the cardiac functions and cell survival without any adverse effects. To further explore the mechanism by which SFN treated MI mice, oxygen and glucose deprivation (OGD) cells was established as a cellular model for the in vitro study of MI. Knockdown of HSF1 or Nrf2 decreased SFN-induced HSP70 in the OGD cells. Moreover, knockdown of HSP70 blocked the pro-survival and anti-inflammatory effect of SFN for OGD cells. Moreover, HSP70 overexpression was sufficient to decrease pro-inflammatory cytokines and improve cell survival under OGD. Taken together, PMSNs transported sufficient SFN to the infarcted area in MI. We demonstrated that SFN exerted cardioprotective effect toward MI injury by up-regulating HSP70 through Nrf2/HSF1.