title: Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging.
abstract: OBJECTIVE
  Receptor-targeted delivery of imaging and therapeutic agents can lead to enhanced efficacy for both. Multimodality imaging offers unique advantages over traditional single modality imaging. Tumor marker folate receptor (FR)-targeted fluorescent paramagnetic bimodal liposomes were synthesized to co-deliver paramagnetic and fluorescence agents for magnetic resonance (MR) and optical bimodal imaging contrast enhancement.
  
  
  METHODS
  Fluorescent and paramagnetic bimodal liposomes were synthesized with a mean diameter of 136 nm and a low polydispersity index. The liposomes incorporated folate-PEG(3350)-CHEMS for FR targeting, Gd(III)[N,N-Bis-stearylamidomethyl-N'-amidomethyl]diethylenetriamine tetraacetic acid (Gd-DTPA-BSA) for MR contrast, and calcein for fluorescence. To determine the specificity and efficiency of delivery, the liposomes were evaluated in FR-positive KB and HeLa cells and FR-negative A549 cells, which were analyzed by fluorescence microscopy, magnetic resonance imaging (MRI), and flow cytometry (FCM).
  
  
  RESULTS
  FR-specific and efficient cellular uptake of the FR-targeted bimodal liposomes was confirmed by fluorescence microscopy and by FCM. The mean fluorescence intensity (MFI) of KB cells treated with FR-targeted liposomes was 45× that of cells treated with nontargeted liposomes, and 18× that of cells treated with FR-targeted liposomes and excess folic acid (FA). The MFI of HeLa cells treated with targeted liposomes was 33× that of nontargeted liposomes, and was 16× that of the mixture of targeted liposomes and free FA. In contrast, the MFI of A549 cells treated with FR-targeted liposomes was nearly the same as those treated with nontargeted liposomes. The T(1)-weighted MR images of HeLa and KB cells incubated with FR-targeted liposomes had much higher signal intensity than those treated with nontargeted liposomes or free Gd-DTPA. Furthermore, the FR-targeting effect could be blocked by excess free FA.
  
  
  CONCLUSIONS
  FR-targeted fluorescent paramagnetic bimodal liposomes provided a novel platform for bimodal tumor imaging and theranostic delivery.
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Chang
authors.initials: C
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002788:Cholesterol Esters / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D002788:Cholesterol Esters; D005452:Fluoresceins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D005492:Folic Acid; D019786:Gadolinium DTPA; C013440:cholesteryl succinate; C007740:fluorexon
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