A natural nano-platform: Advances in drug delivery system with recombinant high-density lipoprotein

Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery. High-density lipoprotein (HDL), a natural lipid-protein complex, plays important roles in physiological activities, particularly in reverse cholesterol transport (RCT) and be closely associated with atherosclerotic cardiovascular diseases. Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers. Recombinant HDLs (rHDLs) have been used to encapsulate substances such as small interfering RNA (siRNA), drugs, and contrast agents, fully utilizing the biocompatibility and targeting ability of rHDL in the body and providing new strategies for drug delivery and disease treatment. In this review, we discussed in detail the basic principles of HDL as a drug delivery system, the mechanisms of targeted drug delivery, and several methods for preparing HDL nanoparticles. Afterward, we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases, cancer treatment (such as glioblastoma, breast cancer, hepatocellular carcinoma and urologic cancers) and some other fields. Finally, we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies. Through a review and summary of these research advances, we aim to fully understand the potential of HDL as a drug carrier in clinical applications, providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.