期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 571, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118706
关键词
Sialic acid; Peripheral blood monocytes; Tumor-associated macrophages; Cancer immunotherapy
资金
- National Natural Science Foundation of China [81703456, 81373334]
- China Grand Enterprises, Inc. (Beijing, China)
Mononuclear phagocytes are efficient drug delivery targets for cancers owing to their cancerous tissue-accumulating nature. As receptors of sialic acid, Siglecs (sialic acid-binding immunoglobulin-type lectins) are noticeably found on peripheral blood monocytes (PBMs) and tumor-associated macrophages (TAMs), which renew by the differentiation of recruited PBMs at the tumor site and positively correlate with tumor growth. Given this, a sialic acid-octadecylamine conjugate (SA-ODA) was synthesized and then modified on the surface of liposomal epirubicin (EPI-SAL) as a potent tumor-targeting delivery strategy. A cellular uptake assay indicated that SA-modified liposomes provided improved distribution of the drug in both PBMs and TAMs. Pharmacodynamic tests demonstrated that the antitumor efficacy of the EPI-SAL group was better than that of the other groups, owing to both inhibition of TAMs by EPI-SAL, and high-efficiency targeting of PBMs by EPI-SAL, after which PBMs containing EPI-SAL were recruited to the tumor site and then killed by EPI. Thus, an SA-based targeted delivery strategy effectively interdicted the generation of TAMs. Our research provides the feasibility of the SA-ODA decorated liposome as an active carrier for cancer immunotherapy.
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