title: Selective targeting of microglia by quantum dots.
abstract: BACKGROUND
  Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.
  
  
  METHODS
  Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.
  
  
  RESULTS
  In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.
  
  
  CONCLUSIONS
  These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.
authors.affiliation: Gladstone Institute of Neurological Disease, 1650 Owens St., San Francisco, CA 94158, USA.
authors.forename: S Sakura
authors.initials: SS
authors.lastname: Minami
authors.forename: Binggui
authors.initials: B
authors.lastname: Sun
authors.forename: Ketul
authors.initials: K
authors.lastname: Popat
authors.forename: Tiina
authors.initials: T
authors.lastname: Kauppinen
authors.forename: Mike
authors.initials: M
authors.lastname: Pleiss
authors.forename: Yungui
authors.initials: Y
authors.lastname: Zhou
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ward
authors.forename: Paul
authors.initials: P
authors.lastname: Floreancig
authors.forename: Lennart
authors.initials: L
authors.lastname: Mucke
authors.forename: Tejal
authors.initials: T
authors.lastname: Desai
authors.forename: Li
authors.initials: L
authors.lastname: Gan
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D002966:Clathrin / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D000922:Immunotoxins / Q000494:pharmacology; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011069:Poly I / Q000494:pharmacology; D045663:Quantum Dots; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000235:genetics; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D013238:Stereotaxic Techniques; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D016229:Amyloid beta-Peptides; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; D002966:Clathrin; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D000922:Immunotoxins; D008351:Mannans; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D019707:Receptors, Chemokine; D054789:Ribosome Inactivating Proteins, Type 1; C075222:amyloid beta-protein (1-42); D049452:Green Fluorescent Proteins; D011069:Poly I; D000076985:Saporins