Hypothermia-Triggered Mesoporous Silica Particles for Controlled Release of Hydrogen Sulfide to Reduce the I/R Injury of the Myocardium
Wenyi Xia, Tao Yan, Lianlei Wen, Shijie Zhu, Yin Wang, Miao Zhu, Meidong Lang, Chunsheng Wang, Changfa Guo
Abstract
Despite the fact that heart transplantation (HTx) is a relatively mature procedure, heart ischemic and reperfusion (I/R) injury during HTx remains a challenge. Even after a successful operation, the heart will be at risk of primary graft failure and mortality during the first year. In this study, temperature-sensitive polymer poly(N-n-propylacrylamide-co-N-tert-butyl acrylamide) (PNNTBA) was coated on diallyl trisulfide (DATS)-loaded mesoporous silica nanoparticles (DATS-MSN) to synthesize hypothermia-triggered hydrogen sulfide (H2S) releasing particles (HT-MSN). Because the PNNTBA shell dissolves in phosphate-buffered saline at 4 °C, the loaded DATS could continuously release H2S within 6 h when activated by glutathione (GSH). Furthermore, after co-culturing biocompatible HT-MSN with cardiomyocytes, H2S released from HT-MSN at 4 °C was found to protect cardiomyocytes from ischemic and reperfusion (I/R) injury. In detail, the rate of cell apoptosis and lactate dehydrogenase activity was decreased, as manifested by increased BCL-2 expression and decreased BAX expression. More importantly, in an isolated heart preservation experiment, HT-MSN demonstrated potent protection against cardiac I/R injury and reduced expression of inflammatory factors TNF-α and IL-1β. This study provided a new method for the controlled release of H2S by the donor and myocardial protection from I/R injury.