Probing in vivo drug release of macrophage-targeting liposomes

Macrophages can internalize liposomes and disrupt them to facilitate drug release in the body. However, the effect of targeting liposomes to macrophages on in vivo drug release remains unclear. In this study, we compared the in vivo drug release from macrophage-targeting liposomes (modified with 1,2-distearoyl phosphatidylserine, PS) and PEGylated liposomes in 4 T1 breast tumor-bearing mice. The macrophage-targeting capability of PS-modified liposomes was confirmed by their significantly enhanced cellular uptake in macrophages compared to that of PEGylated liposomes. In vivo drug release studies showed that PS-modified liposomes exhibited higher drug release in various tissues than that of PEGylated liposomes, suggesting that macrophages facilitate the release of the drug from liposomes in the body. Despite a higher percentage of drug release in the tumor, the PS-modified liposomes did not improve antitumor activity compared to PEGylated liposomes due to their rapid clearance. These results suggest that targeting liposomes to macrophages can enhance in vivo drug release but fail to increase antitumor activity due to low tumor selectivity. Therefore, selectively targeting liposomes to tumor-associated macrophages is essential for boosting antitumor effects.