The LyP-1 cyclic peptide modified mesoporous polydopamine nanospheres for targeted delivery of triptolide regulate the macrophage repolarization in atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease that leads to the formation of atherosclerotic plaques in arterial walls, which can eventually result in cardiovascular diseases. It has been confirmed that the imbalance in the polarization of M1-type pro-inflammatory and M2-type anti-inflammatory macrophages in AS plaques is closely related to plaque instability and the development of cardiovascular diseases like AS-related heart and cerebrovascular diseases. Triptolide (TP) is a promising drug for the treatment of AS due to its anti-inflammatory and anti-proliferative effects. However, its poor solubility and lack of specificity limit its clinical application. We developed a targeted delivery system for TP to M1-type macrophages using mesoporous polydopamine (MPDA) nanospheres modified with the LyP-1 peptide. We then observed the performance of this targeted delivery system and explored its regulatory effects on macrophage polarization in AS. The results showed that the LYP-1-modified MPDA-TP delivery system had an average encapsulation rate of 66.5%, a drug loading capacity of 4.5%, and an average diameter of 250 nm. It exhibited excellent targeting ability and drug release rate towards target cells. LYP-MPDA-TP was capable of inhibiting the proportion of M1 macrophages induced by oxidized low-density lipoprotein stimulation in mouse macrophages, promoting apoptosis in M1-type macrophages significantly, and demonstrating a significant inhibitory effect on AS in experimental animals. The LYP-1 peptide-modified MPDA delivery system provides a new approach for TP treatment of AS and an important theoretical basis and methodological reference for the design of targeted delivery systems for anti-AS nanoparticles.