title: Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice.
abstract: The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33+/-7 microg Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT.
authors.affiliation: Center for Pharmaceutical Science and Technology, Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 907 Rose Street, Lexington, KY 40536-0082, USA.
authors.forename: Moses O
authors.initials: MO
authors.lastname: Oyewumi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yokel
authors.forename: Michael
authors.initials: M
authors.lastname: Jay
authors.forename: Tricia
authors.initials: T
authors.lastname: Coakley
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mumper
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D005682:Gadolinium / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007624:KB Cells; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution / Q000187:drug effects* / Q000502:physiology
chemical_list: D020099:Coated Materials, Biocompatible; D011092:Polyethylene Glycols; D005492:Folic Acid; D005682:Gadolinium