Optimizing the modification density of acid oligopeptides to enhance the bone-targeting activity of liposomes

Acid oligopeptide-modified liposomes show promising bone-targeting activity. However, as the modification density of acid oligopeptides increases, liposomes may exhibit stronger hydroxyapatite (HA)-binding activity and decreased blood pharmacokinetics (PK), exerting opposite effects on their bone-targeted delivery. Nowadays, little research has systematically investigated how modification density of acid oligopeptides affects the bone -targeting activity of liposomes. In the present study, we prepared a library of liposomes with identical lipid components and comparable particle sizes but varied modification densities of glutamic hexapeptide (Glu6, a representative of acid oligopeptides). A higher modification density of Glu6 promoted the liposomes binding to HA. In contrast, the high-density Glu6-induced highly negative surface charge stimulated macrophage-mediated phagocytosis of the liposomes, leading to reduced blood retention. Further, biodistribution data revealed that the liposomes with the highest Glu6 density of 5 mol% (5%e-Lip) exerted the strongest bone-targeting activity because their outstanding HA-binding capability completely overcame their reduced blood PK. Moreover, a hemolysis assay showed that the optimized formulation, 5%e-Lip, had good biocompatibility via systemic in-jection. Overall, these results suggest that the higher modification density of acid oligopeptides facilitated stronger bone-targeting activity of the liposomes, providing a basis for the development of efficient bone -targeting liposomal nanoplatforms for bone disease treatment in the future.

Automated summary

This study systematically investigated the effects of modification density of acid oligopeptides on the bone-targeting activity of liposomes. The results showed that a higher modification density promoted the binding of liposomes to hydroxyapatite, but also increased macrophage-mediated phagocytosis and decreased blood retention. The liposomes with the highest modification density exhibited the strongest bone-targeting activity.