title: Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells.
abstract: OBJECTIVE
  In this work we specifically investigate the molecular weight (Mw) dependent combinatorial properties of hyaluronic acid (HA) for exhibiting stealth and targeting properties using different Mw HA nanoshells to tune nanoparticle retargeting to CD44-expressing cancer cells.
  
  
  METHODS
  HA of different Mw was covalently grafted onto model polystyrene nanoparticles and advanced surface analysis by X-ray photoelectron spectroscopy performed to quantify and evaluate the effect of the coating procedure. Specific CD44-mediated retargeting was investigated by flow cytometry and confocal microscopy using isogenic D44-deficient and CD44-expressing MCF-7 breast adenocarcinoma cells.
  
  
  RESULTS
  Surface analysis demonstrated effective surface coating with 33, 260 and 900 kDa HA resulting in increased colloidal stability and highly negative surface charge due to presentation of up to 4.7% carboxyl groups that indicates an extended and non-constricted HA polymer surface. Reduced non-specific particle interaction in CD44(-) cells was shown for all HA nanoshells but CD44-dependent cellular retargeting and internalization in CD44(+) cells was highly dependent on the coating HA Mw properties.
  
  
  CONCLUSIONS
  The combination of advanced surface characterization and evaluation of particle interactions in isogenic cells with and without CD44 receptor demonstrates direct evidence for the dual capacity of HA for stealth and CD44-mediated retargeting tunable by the HA molecular weight.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, Building 1593, room 329, 8000, Aarhus, Denmark.
authors.forename: Morten F
authors.initials: MF
authors.lastname: Ebbesen
authors.forename: Morten Tj
authors.initials: MT
authors.lastname: Olesen
authors.forename: Mikkel C
authors.initials: MC
authors.lastname: Gjelstrup
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Pakula
authors.forename: Esben Ku
authors.initials: EK
authors.lastname: Larsen
authors.forename: Irene M
authors.initials: IM
authors.lastname: Hansen
authors.forename: Pernille L
authors.initials: PL
authors.lastname: Hansen
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.forename: Birgitte M
authors.initials: BM
authors.lastname: Malle
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Howard
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008970:Molecular Weight; D057145:Nanoshells / Q000737:chemistry*; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D011137:Polystyrenes / Q000737:chemistry*; D013499:Surface Properties
chemical_list: C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D011137:Polystyrenes; D006820:Hyaluronic Acid