Hyaluronan nanoparticles selectively target plaque-associated macrophages and improve plaque stability in atherosclerosis Journal Article
| Authors: | Beldman, T. J.; Senders, M. L.; Alaarg, A.; Pérez-Medina, C.; Tang, J.; Zhao, Y.; Fay, F.; Deichmöller, J.; Born, B.; Desclos, E.; van der Wel, N. N.; Hoebe, R. A.; Kohen, F.; Kartvelishvily, E.; Neeman, M.; Reiner, T.; Calcagno, C.; Fayad, Z. A.; de Winther, M. P. J.; Lutgens, E.; Mulder, W. J. M.; Kluza, E. |
| Article Title: | Hyaluronan nanoparticles selectively target plaque-associated macrophages and improve plaque stability in atherosclerosis |
| Abstract: | Hyaluronan is a biologically active polymer, which can be formulated into nanoparticles. In our study, we aimed to probe atherosclerosis-associated inflammation by using hyaluronan nanoparticles and to determine whether they can ameliorate atherosclerosis. Hyaluronan nanoparticles (HA-NPs) were prepared by reacting amine-functionalized oligomeric hyaluronan (HA) with cholanic ester and labeled with a fluorescent or radioactive label. HA-NPs were characterized in vitro by several advanced microscopy methods. The targeting properties and biodistribution of HA-NPs were studied in apoe-/- mice, which received either fluorescent or radiolabeled HA-NPs and were examined ex vivo by flow cytometry or nuclear techniques. Furthermore, three atherosclerotic rabbits received 89Zr-HA-NPs and were imaged by PET/MRI. The therapeutic effects of HA-NPs were studied in apoe-/- mice, which received weekly doses of 50 mg/kg HA-NPs during a 12-week high-fat diet feeding period. Hydrated HA-NPs were ca. 90 nm in diameter and displayed very stable morphology under hydrolysis conditions. Flow cytometry revealed a 6- to 40-fold higher uptake of Cy7-HA-NPs by aortic macrophages compared to normal tissue macrophages. Interestingly, both local and systemic HA-NP-immune cell interactions significantly decreased over the disease progression. 89Zr-HA-NPs-induced radioactivity in atherosclerotic aortas was 30% higher than in wild-type controls. PET imaging of rabbits revealed 6-fold higher standardized uptake values compared to the muscle. The plaques of HA-NP-treated mice contained 30% fewer macrophages compared to control and free HA-treated group. In conclusion, we show favorable targeting properties of HA-NPs, which can be exploited for PET imaging of atherosclerosis-associated inflammation. Furthermore, we demonstrate the anti-inflammatory effects of HA-NPs in atherosclerosis. © 2017 American Chemical Society. |
| Keywords: | flow cytometry; fluorescence; inflammation; pathology; atherosclerosis; radioactivity; nanoparticles; pet imaging; hyaluronic acid; macrophages; mammals; diseases; hyaluronan; anti-inflammatory effects; antiatherogenic therapy; hyaluronan nanoparticles |
| Journal Title: | ACS Nano |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 1936-0851 |
| Publisher: | American Chemical Society |
| Date Published: | 2017-06-27 |
| Start Page: | 5785 |
| End Page: | 5799 |
| Language: | English |
| DOI: | 10.1021/acsnano.7b01385 |
| PROVIDER: | scopus |
| PMCID: | PMC5492212 |
| PUBMED: | 28463501 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work