title: Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with tumour cells.
abstract: Folic acid has been previously demonstrated to mediate intracellular nanoparticle uptake. Here, we investigated cellular uptake of folic acid-conjugated human serum albumin nanoparticles (HSA NPs). HSA NPs were prepared by desolvation and stabilised by chemical cross-linking with glutaraldehyde. Folic acid was covalently coupled to amino groups on the surface of HSA NPs by carbodiimide reaction. Preparation resulted in spherical HSA NPs with diameters of 239 ± 26 nm. As shown by size exclusion chromatography, 7.40 ± 0.90 μg folate was bound per mg HSA NPs. Cellular NP binding and uptake were studied in primary normal human foreskin fibroblasts (HFFs), the human neuroblastoma cell line UKF-NB-3, and the rat glioblastoma cell line 101/8 by fluorescence spectrophotometry, flow cytometry, and confocal laser scanning microscopy. Covalent conjugation of folic acid to HSA NPs increased NP uptake into cancer cells but not into HFFs. Free folic acid interfered with cancer cell uptake of folic acid-conjugated HSA NPs but not with uptake of folic acid-conjugated HSA NPs into HFFs. These data suggest that covalent linkage of folic acid can specifically increase cancer cell HSA NP uptake.
authors.affiliation: Institute of Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, D-60438 Frankfurt am Main, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Florian
authors.initials: F
authors.lastname: Rothweiler
authors.forename: Thomas
authors.initials: T
authors.lastname: Knobloch
authors.forename: Patchima
authors.initials: P
authors.lastname: Sithisarn
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012709:Serum Albumin; D005492:Folic Acid