Interaction of self-assembled galactomannan-based polymeric nanocarriers with a murine macrophage cell line in vitro

Macrophages are phagocytic cells that form one of the first lines of defense in our innate immune system and are involved in diverse important biological pathways, such as the immune response, metabolism, cancer, fibrosis and wound healing. Macrophages are activated in a dynamic response to stimuli combinations to acquire specialized functional phenotypes and enhanced biological activity and can undergo classical or alternative activation also known as M1 (pro-inflammatory response) and M2 (anti-inflammatory response), respectively. These heterogeneous functions of macrophages in human immune systems have renewed the interest to target drugs that modulate their activity. Lectin-like receptors (LLRs) are sugar-binding transmembrane proteins that are highly expressed in macrophages. Thus, LLRs have been an extensively investigated cellular structure to target drugs to macrophages. Conjugation of sugars that bind LLRs is one of the approaches to actively target drugs to macrophages. Galactomannan – a polysaccharide of mannose and galactose - has been demonstrated to interact with LLRS in murine macrophages and increase the uptake of polymeric micelles, a type of drug nanocarrier generated by the self-assembly of polymeric amphiphiles [1]. Aiming to develop a more versatile strategy to target macrophages in different body sites, in this work, we report on the synthesis of a novel type of self-assembled amphiphilic polymeric nanoparticle based on the hydrophobization of hydrolyzed galactomannan with poly(methyl methacrylate) (PMMA). After a thorough characterization of the nanoparticle properties, the interaction with a murine cell line was assessed in vitro.

Acknowledgements. This work was funded by the European Union`s - Seventh Framework Programme under grant agreement #612765-MC-NANOTAR.

References

1. Moretton MA, Chiappetta DA, Andrade F, das Neves J, Ferreira D, Sarmento B, Sosnik A, Hydrolyzed galactomannan-modified nanoparticles and flower-like polymeric micelles for the active targeting of rifampicin to macrophages, J Biomed Nanotechnol 9, 1076-1087 (2013).