title: Targeting cells of the immune system: mannosylated HPMA-LMA block-copolymer micelles for targeting of dendritic cells.
abstract: BACKGROUND
  Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy.
  
  
  METHODS
  Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP. Both types of copolymers were conjugated with D-mannose to target the mannose receptor as expressed by DCs and macrophages. The extent and specificity of micelle binding and activation of APCs was monitored using mouse spleen cells and bone marrow-derived DC (BMDC).
  
  
  RESULTS
  Nontargeting HPMA-LMA statistical copolymers showed strong unspecific cell binding. HPMA-LMA block copolymers bound DC only when conjugated with mannose, and in a mannose receptor-specific manner. Mannosylated HPMA-LMA block copolymers were internalized by DC. DC-targeting HPMA-LMA block copolymers mediated DC activation when loaded with L18-MDP.
  
  
  CONCLUSIONS
  Mannosylated HPMA-LMA block copolymers are a promising candidate for the delvopment of DC-targeting nanovaccines.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mohr
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131 Mainz, Germany.
authors.forename: Cinja
authors.initials: C
authors.lastname: Kappel
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kramer
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131 Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008358:Mannose / Q000737:chemistry*; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D058105:Polymerization; D011108:Polymers; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013499:Surface Properties
chemical_list: D008689:Methacrylates; D008823:Micelles; D011108:Polymers; C115846:dodecyl methacrylate; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035295:6-O-stearoyl-N-acetylmuramyl-alanylisoglutamine; D008358:Mannose; C032802:hydroxypropyl methacrylate
keywords: HPMA block copolymer; dendritic cell; immune system; mannose as targeting ligand