title: Lysosome-targeted octadecyl-rhodamine B-liposomes enhance lysosomal accumulation of glucocerebrosidase in Gaucher's cells in vitro.
abstract: OBJECTIVE
  We hypothesized that liposomes modified with lysosomotropic octadecyl-rhodamine B (Rh) and loaded with therapeutic glucocerebroside velaglucerase alfa (VPRIV™) will improve lysosomal delivery of the enzyme into Gaucher's cells.
  
  
  METHODS
  Confocal microscopy and flow cytometry were used to evaluate the ability of Rh-modified liposomes loaded with VPRIV to improve the lysosomal targeting in monocyte-derived macrophages and Gaucher's fibroblasts.
  
  
  RESULTS
  Confocal microscopy demonstrated that Rh-modified liposomes localized primarily in the lysosomes. As confirmed by flow cytometry using specific substrate 5-(pentafluorobenzoylamino)fluorescein diglucoside, intralysosomal accumulation of VPRIV in the cells treated with Rh-modified liposomes was significantly increased (up to 68%) relative to the cells treated with plain liposomes or free VPRIV.
  
  
  CONCLUSIONS
  Rh-modified lysosomotropic liposomes can improve lysosomal accumulation of liposomal enzymes both in nonphagocytic Gaucher's fibroblasts and phagocytic monocyte-derived macrophages.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, 140 Fenway Street, Boston, MA 02115, USA.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Thekkedath
authors.forename: Alexander
authors.initials: A
authors.lastname: Koshkaryev
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005776:Gaucher Disease / Q000201:enzymology / Q000378:metabolism; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry*; D018613:Microscopy, Confocal; D012235:Rhodamines / Q000737:chemistry*
chemical_list: D008081:Liposomes; D012235:Rhodamines; C425723:octadecylrhodamine B; D005962:Glucosylceramidase