Breast cancer metastasis is an important cause of death in patients with
breast cancer and is closely related to
circulating tumor cells (CTCs) and the metastatic microenvironment. As the most infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs), which highly express
sialic acid (SA) receptor (Siglec-1), are closely linked to
tumor progression and
metastasis. Furthermore, the surface of CTCs also highly expressed receptor (
Selectin) for SA. A targeting
ligand (SA-CH), composed of SA and
cholesterol, was synthesized and modified on the surface of
epirubicin (EPI)-loaded
liposomes (EPI-SL) as an effective targeting delivery system.
Liposomes were evaluated for characteristics, stability, in vitro release, cytotoxicity, cellular uptake, pharmacokinetics,
tumor targeting, and pharmacodynamics. In vivo and in vitro experiments showed that EPI-SL enhanced EPI uptake by TAMs. In addition, cellular experiments showed that EPI-SL could also enhance the uptake of EPI by 4T1 cells, resulting in cytotoxicity second only to that of EPI
solution. Pharmacodynamic experiments have shown that EPI-SL has optimal
tumor inhibition with minimal toxicity, which can be ascribed to the fact that EPI-SL can deliver drugs to
tumor based on TAMs and regulate TME through the depletion of TAMs. Our study demonstrated the significant potential of SA-modified
liposomes in antitumor
metastasis. Schematic diagram of the role of SA-CH modified EPI-loaded
liposomes in the model of
breast cancer metastasis.