Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging.
Folate-targeted bimodal paramagnetic and fluorescent liposomes were developed and showed enhanced accumulation in a folate receptor expressing tumor model. These bimodal liposomes were composed of both a paramagnetic and a fluorescent lipid, and utilized a PEG-lipid amphiphile for prolonged in vivo circulation. The particles were formulated to ensure a size distribution of approximately 100 nm with a low polydispersity index. IGROV-1 cells were used to induce tumors in nude Balb/c mice, and the folate-targeted liposomes were injected intravenously. Rapid accumulation of the folate-targeted liposomes within the tumor tissue compared to nontargeted liposomes was observed. Furthermore, folate-labeled liposomes showed a 4-fold increase in tumor T(1) signal intensity at just 2 h postinjection with similar results being obtained for the nontargeted liposomes only 24 h postinjection. In addition, the folate-targeted liposomes were injected at half the nontargeted liposome dose, further demonstrating their effectiveness. Histological analysis of sectioned tumor slices revealed distinct fluorescence patterns between the targeted and nontargeted systems, with a more localized and hyperintense fluorescence signal observed from tumor sections post-folate-targeted liposome injections. These results demonstrate the effectiveness of folate targeting for dynamic real-time solid tumor MRI and provide insight into kinetics of targeted and nontargeted nanoparticles to solid tumors.
Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College London, UK. Nazila.Kamaly@imperial.ac.uk
Nazila
N
Kamaly
Tammy
T
Kalber
Maya
M
Thanou
Jimmy D
JD
Bell
Andrew D
AD
Miller
D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*
D002352:Carrier Proteins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D008024:Ligands; D008081:Liposomes; D011956:Receptors, Cell Surface; D005682:Gadolinium