Thermo-responsive co-delivery of therapeutic drug and Gasotransmitter for treating atherosclerosis

Targeted delivery of therapeutics demonstrates great potential for the treatment of atherosclerosis (AS). However, the uncontrolled cargo release from nanocarriers limits their ability to achieve optimal therapeutic functions and outcomes. Herein, we propose a thermo-responsive phase transformation-based strategy for controlled drug release, enabling precise delivery specifically to atherosclerotic plaque sites. We developed a nanomedicine (PDA@A/G) by encapsulating tetradecanol (TD) with atorvastatin (ATV) and hydrogen sulfide (H 2 S) donor GYY4137 into polydopamine (PDA) nanocapsules featuring a small hole. The phase transition of TD from solid to liquid state within the atherosclerotic microenvironment, which has a temperature of approximately 39 °C, triggers the release of H 2 S and ATV. The release of the therapeutic drug and gasotransmitter exerts synergistic effects in regulating oxidative stress, alleviating inflammation, and improving endothelial function, showing dramatic capacity in inhibiting plaque progression. This strategy provides a novel and highly promising paradigm for the development of nanomedicine aimed at the targeted co-delivery of drug and gasotransmitter in AS therapy.