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. 2018 Jul 1:119:159-170.
doi: 10.1016/j.ejps.2018.04.018. Epub 2018 Apr 13.

Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers

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Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers

Sara Nikoofal-Sahlabadi et al. Eur J Pharm Sci. .

Abstract

CpG oligodeoxynucleotides (CpG-ODN), a common immune stimulator and vaccine adjuvant, was reported to switch Tumor Associated Macrophages (TAMs) from M2 to M1 phenotype inducing anti-tumor responses. Liposomes are of the successfully applied carriers for CpG-ODN. The aim of present study was design and preparation of a liposomal formulation containing phosphodiester CpG-ODN, evaluation of its effect on macrophages responses, and subsequent antitumor responses in mice. Liposomal formulations containing phosphodiester CpG-ODN or non-CpG-ODN were prepared and characterized. MTT reduction assay in four different cell lines, uptake, arginase and iNOS activity evaluation in macrophage cell lines, biodistribution study and therapeutic anti-tumor effects of formulations in mice bearing C26 colon carcinoma or B16F0 melanoma were carried out. The size of liposomes containing CpG-ODN was ~200 nm with the encapsulation efficiency of 33%. The iNOS activity assay showed high nitric oxide (NO) level in M2 phenotype of macrophage cell lines treated by liposomes containing CpG-ODN. In mice which received liposomes containing CpG-ODN as a monotherapy, maximum tumor growth delay with remarkable survival improvement was observed compared to control groups. Biodistribution study showed the accumulation of liposomal formulation in tumor micro-environment. In conclusion, considerable anti-tumor responses observed by liposomes containing CpG-ODN was due to enhanced delivery of CpG-ODN to immune cells and subsequent initiation of anti-tumoral immune responses.

Keywords: CpG-ODN; Immunotherapy; Liposome; Tissue distribution; Tumor.

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