Hyaluronic acid immobilized magnetic nanoparticles for active targeting and imaging of macrophages.
Imaging and targeted delivery to macrophages are promising new approaches to study and treat a variety of inflammatory diseases such as atherosclerosis. In this manuscript, we have designed and synthesized iron oxide based magnetic nanoparticles bearing hyaluronic acid (HA) on the surface to target activated macrophages. The HA-coated nanoparticles were prepared through a co-precipitation procedure followed by postsynthetic functionalization with HA and fluorescein. The nanoparticles were characterized by transmission electron microscopy, thermogravimetric analysis, elemental analysis, dynamic light scattering, and high-resolution magic angle spinning NMR and were biocompatible with cells and colloidally stable in the presence of serum. The HA immobilized on the nanoparticles retained their specific biological recognition with the HA receptor CD44, which is present on activated macrophages in high-affinity forms. Cell uptake studies demonstrated significant uptake of HA nanoparticles by activated macrophage cell line THP-1, which enabled magnetic resonance imaging of THP-1 cells. The uptake of nanoparticles was found to be both HA and CD44 dependent. Interestingly, Prussian blue staining showed that the magnetite cores of the HA-coated nanoparticles were only transiently present inside the cells, thus reducing the potential concerns of nanotoxicity. Furthermore, fluorescein on the nanoparticle was found to be delivered to the cell nucleus. Therefore, with further development, these HA functionalized magnetic nanoparticles can potentially become a useful carrier system for molecular imaging and targeted drug delivery to activated macrophages.
Kamat
Medha
M
Department of Chemistry, Michigan State University, East Lansing, 48824, United States.
El-Boubbou
Kheireddine
K
Zhu
David C
DC
Lansdell
Teri
T
Lu
Xiaowei
X
Li
Wei
W
Huang
Xuefei
X
D002460:Cell Line; D005290:Ferric Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D013499:Surface Properties
D005290:Ferric Compounds; C000499:ferric oxide; D006820:Hyaluronic Acid