title: Cell membrane-formed nanovesicles for disease-targeted delivery.
abstract: Vascular inflammation is the underlying component of most diseases. To target inflamed vasculature, nanoparticles are commonly engineered by conjugating antibody to the nanoparticle surface, but this bottom-up approach could affect nanoparticle targeting and therapeutic efficacy in complex, physiologically related systems. During vascular inflammation endothelium via the NF-κB pathway instantly upregulates intercellular adhesion molecule 1 (ICAM-1) which binds integrin β2 on neutrophil membrane. Inspired by this interaction, we created a nanovesicle-based drug delivery system using nitrogen cavitation which rapidly disrupts activated neutrophils to make cell membrane nanovesicles. Studies using intravital microscopy of live mouse cremaster venules showed that these vesicles can selectively bind inflamed vasculature because they possess intact targeting molecules of integrin β2. Administering of nanovesicles loaded with TPCA-1 (a NF-κB inhibitor) markedly mitigated mouse acute lung inflammation. Our studies reveal a new top-down strategy for directly employing a diseased tissue to produce biofunctional nanovesicle-based drug delivery systems potentially applied to treat various diseases.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA.
authors.forename: Dafeng
authors.initials: D
authors.lastname: Chu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA. Electronic address: zhenjia.wang@wsu.edu.
authors.forename: Zhenjia
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011014:Pneumonia / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy; D014699:Venules / Q000187:drug effects / Q000378:metabolism
chemical_list: D000577:Amides; D016328:NF-kappa B; D013876:Thiophenes; D018799:Intercellular Adhesion Molecule-1; C499326:2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide
keywords: Nanovesicles; Targeted drug delivery; Vascular inflammation