Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes

Active-targeting nanomedicine formulations have an intricate in vivo behavior. Nanomedicines developed to target endothelial αvβ3-integrin are recently demonstrated to display extensive uptake by circulating phagocytes. These phagocytes show inherent tumor-homing capacities and therefore are capable...

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Bibliographic Details
Published in:Advanced Science
Main 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, Mulder, Willem JM
Other Authors: Tromsø Research Foundation, Trond Mohn Foundation, Norwegian Research Centre, Central Norway Regional Health Authority
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2021
Subjects:
Arginine
Glycine
Aspartate
Immunotherapy
Inflammation
Intravital microscopy
Nanomedicines
Neutrophils
Phagocyte hitchhiking
Norway
Tromsø
Online Access:https://hdl.handle.net/20.500.12105/14210
https://doi.org/10.1002/advs.202100370
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Summary:Active-targeting nanomedicine formulations have an intricate in vivo behavior. Nanomedicines developed to target endothelial αvβ3-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. This work was supported by the Central Norway Regional Health Authority “Helse Midt-Norge” (A.M.S.: Ph.D. stipend [90062100] and travel grant [90284100]; S.H.: researcher grant [90262100]), the Norwegian Research Council (S.H.: 230788/F20), the Tromsø Research Foundation, and Trond Mohn Foundation (S.H.: 180°N project). Sí

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