title: Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia.
abstract: Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact.
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.|Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.|Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ronnie H
authors.initials: RH
authors.lastname: Fang
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Luk
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ashley V
authors.initials: AV
authors.lastname: Kroll
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Dehaini
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Hyeon Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010980:Platelet Membrane Glycoproteins / Q000008:administration & dosage* / Q000737:chemistry; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D020099:Coated Materials, Biocompatible; D010980:Platelet Membrane Glycoproteins
keywords: Antibody decoy; Autoimmune disease; Biomimetic nanoparticle; Nanosponge; Platelet membrane-coated nanoparticle