Folate-targeted gadolinium-lipid-based nanoparticles as a bimodal contrast agent for tumor fluorescent and magnetic resonance imaging.
To enhance tumor magnetic resonance imaging (MRI) signals via the selective accumulation of contrast agents, we prepared folate-modified gadolinium-lipid-based nanoparticles as MRI contrast agents. Folate-modified nanoparticles were comprised of polyethylene glycol (PEG)-lipid, gadolinium diethylenetriamine pentaacetic acid lipid, cationic cholesterol derivatives, folate-conjugated PEG-lipid, and Cy7-PEG-lipid. Folate receptor-mediated cellular nanoparticle association was examined in KB cells, which overexpress the folate receptor. The biodistribution of nanoparticles after their intravenous injection into KB tumor-bearing mice was measured. Mice were imaged through in vivo fluorescence imaging and MRI 24 h after nanoparticle injection, and the intensity enhancement of the tumor MRI signal was evaluated. Increased cellular association of folate-modified nanoparticles was inhibited by excess free folic acid, indicating that nanoparticle association was folate receptor-mediated. Irrespective of folate modification, the amount of nanoparticles in blood 24 h after injection was ca. 10% of the injected dose. Compared with non-modified nanoparticles, folate-modified nanoparticles exhibited significant accumulation in tumor tissues without altering other biodistribution, as well as enhanced tumor fluorescence and MRI signal intensity. The results support the feasibility of MRI- and in vivo fluorescence imaging-based tumor visualization using folate-modified nanoparticles and provide opportunities to develop folate targeting-based imaging applications.
Institute of Medicinal Chemistry, Hoshi University.
Taro
T
Nakamura
Kumi
K
Kawano
Kouichi
K
Shiraishi
Masayuki
M
Yokoyama
Yoshie
Y
Maitani
D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005260:Female; D058972:Folic Acid Transporters / Q000378:metabolism*; D005682:Gadolinium / Q000097:blood; D006801:Humans; D007624:KB Cells; D008055:Lipids; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods*; D014018:Tissue Distribution
D003287:Contrast Media; D058972:Folic Acid Transporters; D008055:Lipids; D005682:Gadolinium