title: Biodistribution and trafficking of hydrogel nanoparticles in adult mosquitoes.
abstract: BACKGROUND
  Nanotechnology offers great potential for molecular genetic investigations and potential control of medically important arthropods. Major advances have been made in mammalian systems to define nanoparticle (NP) characteristics that condition trafficking and biodistribution of NPs in the host. Such information is critical for effective delivery of therapeutics and molecules to cells and organs, but little is known about biodistribution of NPs in mosquitoes.
  
  
  RESULTS
  PRINT technology was used to construct a library of fluorescently labeled hydrogel NPs of defined size, shape, and surface charge. The biodistribution (organ, tissue, and cell tropisms and trafficking kinetics) of positively and negatively charged 200 nm x 200 nm, 80 nm x 320 nm, and 80 nm x 5000 nm NPs was determined in adult Anopheles gambiae mosquitoes as a function of the route of challenge (ingestion, injection or contact) using whole body imaging and fluorescence microscopy. Mosquitoes readily ingested NPs in sugar solution. Whole body fluorescence imaging revealed substantial NP accumulation (load) in the alimentary tracts of the adult mosquitoes, with the greatest loads in the diverticula, cardia and foregut. Positively and negatively charged NPs differed in their biodistribution and trafficking. Following oral challenge, negatively charged NPs transited the alimentary tract more rapidly than positively charged NPs. Following contact challenge, negatively charged NPs trafficked more efficiently in alimentary tract tissues. Following parenteral challenge, positively and negatively charged NPs differed in tissue tropisms and trafficking in the hemocoel. Injected NPs were also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel into the alimentary tract.
  
  
  CONCLUSIONS
  Herein we have developed a tool box of NPs with the biodistribution and tissue tropism characteristics for gene structure/function studies and for delivery of vector lethal cargoes for mosquito control.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Cynthia C H
authors.initials: CC
authors.lastname: Paquette
authors.affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Yashdeep
authors.initials: Y
authors.lastname: Phanse
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Perry
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Irma
authors.initials: I
authors.lastname: Sanchez-Vargas
authors.affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Airs
authors.affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Dunphy
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Carlson
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Institute for Nanomedicine and Institute for Advanced Materials, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, United States of America; Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
authors.affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Lyric C
authors.initials: LC
authors.lastname: Bartholomay
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Beaty
mesh_terms: D000818:Animals; D000852:Anopheles / Q000378:metabolism*; D001179:Arthropod Vectors; D004337:Drug Carriers / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000493:pharmacokinetics*; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D058726:Nanoconjugates; D053758:Nanoparticles / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D007306:Insecticides; D058726:Nanoconjugates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate