title: Biocompatible and pH-sensitive PLGA encapsulated MnO nanocrystals for molecular and cellular MRI.
abstract: Inorganic manganese-based particles are becoming attractive for molecular and cellular imaging, due to their ability to provide bright contrast on MRI, as opposed to the dark contrast generated from iron-based particles. Using a single emulsion technique, we have successfully fabricated pH-sensitive poly(lactic-co-glycolic acid) (PLGA)-encapsulated manganese oxide (MnO) nanocrystals. Two classes of particles were fabricated at ∼140 nm and 1.7 μm and incorporated 15 to 20 nm MnO nanocrystals with high encapsulation efficiencies. Intact particles at physiological pH cause little contrast in MRI, but following endocytosis into low pH compartments within the cells, the particles erode and MnO dissolves to release Mn(2+). This causes the cells to appear bright on MR images. The magnitude of the change in MRI properties is as high as 35-fold, making it the most dynamic "smart" MRI contrast agent yet reported. Possible applications of these MnO particles include slow release Mn(2+), tumor targeting, and confirmation of cell uptake.
authors.affiliation: Department of Biomedical Engineering, Yale University, 300 Cedar Street, New Haven, Connecticut 06520, United States.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Bennewitz
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Lobo
authors.forename: Michael K
authors.initials: MK
authors.lastname: Nkansah
authors.forename: Gözde
authors.initials: G
authors.lastname: Ulas
authors.forename: Gary W
authors.initials: GW
authors.lastname: Brudvig
authors.forename: Erik M
authors.initials: EM
authors.lastname: Shapiro
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D017895:Manganese Compounds / Q000493:pharmacokinetics*; D049329:Nanostructures / Q000737:chemistry; D010087:Oxides / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D017895:Manganese Compounds; D010087:Oxides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C027424:manganese oxide