Background: The purpose of our study was to find a novel targeted imaging and drug delivery vehicle
for inflammatory bowel disease (IBD). IBD is a common and troublesome disease that still lacks effective therapy
and imaging options. As an attempt to improve the disease treatment, we tested αMSH for the targeting of
nanoliposomes to IBD sites. αMSH, an endogenous tridecapeptide, binds to the melanocortin-1 receptor (MC1-R)
and has anti-inflammatory and immunomodulating effects. MC1-R is found on macrophages, neutrophils and the
renal tubule system. We formulated and tested a liposomal nanoparticle involving αMSH in order to achieve a
specific targeting to the inflamed intestines.
Methods: NDP-αMSH peptide conjugated to Alexa Fluor™ 680 was linked to the liposomal membrane via NSuccinyl
PE and additionally loaded into the lumen of the liposomes. Liposomes without the αMSH-conjugate
and free NDP-αMSH were used as a control. The liposomes were also loaded with ICG to track them. The
liposomes were tested in DSS treated mice, which had received DSS via drinking water order to develop a model
IBD. Inflammation severity was assessed by the Disease Activity Index (DAI) score and ex vivo histological
CD68 staining of samples taken from different parts of the intestine. The liposome targeting was analyzed by
analyzing the ICG and ALEXA 680 fluorescence in the intestine compared to the biodistribution.
Results: NPD-αMSH was successfully labeled with Alexa and retained its biological activity. Liposomes were
identified in expected regions in the inflamed bowel regions and in the kidneys, where MC1-R is abundant. In
vivo liposome targeting correlated with the macrophage concentration at the site of the inflammation supporting
the active targeting of the liposomes through αMSH. The liposomal αMSH was well tolerated by animals.
Conclusion: This study opens up the possibility to further develop an αMSH targeted theranostic delivery to
different clinically relevant applications in IBD inflammation but also opens possibilities for use in other inflammations
like lung inflammation in Covid 19.