Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes. Issue 13 (3rd May 2021)

• Record Type: Journal Article
• Authors: Sofias, Alexandros Marios; Bjørkøy, Geir; Ochando, Jordi; Sønstevold, Linda; Hegvik, Maria; Davies, Catharina de Lange; Haraldseth, Olav; Lammers, Twan; Mulder, Willem J. M.; Hak, Sjoerd
• Is Part Of: Advanced science. Volume 8:Issue 13(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-03
• Subjects: arginine–glycine–aspartate -- immunotherapy -- inflammation -- intravital microscopy -- nanomedicines -- neutrophils -- phagocyte hitchhiking; Science -- Periodicals; 505
• DOI: 10.1002/advs.202100370
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Active‐targeting nanomedicine formulations have an intricate in vivo behavior. Nanomedicines developed to target endothelial α v β 3 ‐integrin are recently demonstrated to display extensive uptake by circulating phagocytes. These phagocytes show inherent tumor‐homing capacities and therefore are capable of actively delivering the endocytosed nanomaterial in lesions. Here, the targeting kinetics and mechanisms of cyclic arginine–glycine–aspartate (cRGD)‐decorated lipid nanoparticles (NPs) toward activated vasculature in inflamed lesions during wound healing are studied. The cRGD‐NP targeting toward inflamed lesions is identified to be mechanistically similar to the NP accumulation in cancerous lesions. Through a complementary experimental approach, it is observed that circulating phagocytes engage cRGD‐NPs and are subsequently homed to the inflamed endothelium. The inflammation‐associated phagocytes remain static among endothelial cells upon targeting, resulting in the extensive presence of cRGD‐NP‐positive phagocytes in the angiogenic vessels. Hence, phagocytic immune cells contribute to cRGD‐NP targeting toward angiogenesis. This mechanistic study underlines the need for detailed investigations of NP in vivo behavior. This is critically important for the realization of NPs potential as advanced (immunological) therapeutic agents. Abstract : Decoration of lipid nanoparticles (NPs) with cyclic arginine–glycine–aspartate (cRGD) peptides results in extensive targeting of these NPs to neutrophils and monocytes in vivo. This enables the hitchhiking of cRGD‐NPs with myeloid immune cells toward inflammatory lesions. The discovery of such a targeting mechanism may open up possibilities for therapeutic or diagnostic use of cRGD‐NPs targeting pro‐inflammatory myeloid cells.