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

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.

• Authors: Sara Nikoofal-Sahlabadi, Maryam Matbou Riahi, Kayvan Sadri, Ali Badiee, Amin Reza Nikpoor, Mahmoud Reza Jaafari
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 119 Pg. 159-170 (Jul 01 2018) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 29660463 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• CPG-oligonucleotide
• Liposomes
• Oligodeoxyribonucleotides
• Nitric Oxide
• Arginase

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacokinetics, therapeutic use)
• Animals
• Arginase (metabolism)
• Cell Line
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Liposomes
• Macrophages (drug effects, metabolism)
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasms (drug therapy, metabolism)
• Nitric Oxide (metabolism)
• Oligodeoxyribonucleotides (administration & dosage, pharmacokinetics, therapeutic use)
• Tissue Distribution