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Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles
Link to Journal Abstract
Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.
Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. This report describes the computational design of "Self" peptides from human CD47 and then their synthesis and attachment to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47.
Peer Reviewed Journal Article
Exposure Or Hazard Target
Method Of Study
Risk Exposure Group
Science, 339(6122): 971-975 (February 2013)
Rodriguez PL, Harada T, Christian DA, Pantano DA, Tsai RK, Discher DE
Last updated on February 22, 2013
This work is supported in part by the Nanoscale Science and Engineering Initiative of the National Science Foundation
under NSF Award Number EEC-0118007.
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