title: Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles.
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.
authors: Molecular and Cell Biophysics and NanoBioPolymers Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Pia L
authors: PL
authors: Rodriguez
authors: Takamasa
authors: T
authors: Harada
authors: David A
authors: DA
authors: Christian
authors: Diego A
authors: DA
authors: Pantano
authors: Richard K
authors: RK
authors: Tsai
authors: Dennis E
authors: DE
authors: Discher
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001324:Autoantigens; D001775:Blood Circulation; D051928:CD47 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis; D009369:Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D010316:Particle Size; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D001324:Autoantigens; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D010446:Peptide Fragments; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D017239:Paclitaxel