Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/14210
Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes
Adv. Sci.2021;8 :2100370
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.
Arginine | Glycine | Aspartate | Immunotherapy | Inﬂammation | Intravital microscopy | Nanomedicines | Neutrophils | Phagocyte hitchhiking
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