title: Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.
abstract: Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Gilbert
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: School of Pharmacy, Keck Graduate Institute, 535 Watson Dr., Claremont, CA 91711, United States.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Cohen
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Rubner
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, United States. Electronic address: samir@engineering.ucsb.edu.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects*; D011108:Polymers / Q000737:chemistry; D011247:Pregnancy
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D011108:Polymers
keywords: Cell therapies; Cell-mediated drug delivery; Inflammation; Layer-by-layer; Microparticles; Monocytes