Terminating the renewal of tumor-associated macrophages: a sialic acid-based targeted delivery strategy for cancer immunotherapy

Publication date: Available online 5 October 2019Source: International Journal of PharmaceuticsAuthor(s): Junqiang Ding, Dan Zhao, Yawei Hu, Mingqi Liu, Xinrui Liao, Bowen Zhao, Xinrong Liu, Yihui Deng, Yanzhi SongAbstractMononuclear 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.Graphical ab...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research