title: Nanoparticle biointerfacing by platelet membrane cloaking.
abstract: Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Che-Ming J
authors.initials: CM
authors.lastname: Hu
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Ronnie H
authors.initials: RH
authors.lastname: Fang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Kuei-Chun
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.|Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Luk
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Soracha
authors.initials: S
authors.lastname: Thamphiwatana
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Dehaini
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Phu
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Pavimol
authors.initials: P
authors.lastname: Angsantikul
authors.affiliation: Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Cindy H
authors.initials: CH
authors.lastname: Wen
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Ashley V
authors.initials: AV
authors.lastname: Kroll
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Cody
authors.initials: C
authors.lastname: Carpenter
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Manikantan
authors.initials: M
authors.lastname: Ramesh
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Qu
authors.affiliation: Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Sherrina H
authors.initials: SH
authors.lastname: Patel
authors.affiliation: Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: William
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Hofman
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA.|Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA.|Veterans Administration Healthcare System, San Diego, California 92093, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
authors.affiliation: Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA.|Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000166:cytology*; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D023903:Coronary Restenosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010973:Platelet Adhesiveness; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000166:cytology / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D053835:Unilamellar Liposomes / Q000737:chemistry; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D043823:Taxoids; D053835:Unilamellar Liposomes; D000077143:Docetaxel; D014640:Vancomycin; D003094:Collagen