Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.
A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.
Liu
Jian
J
Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku Kyoto 606-8507, Japan.
Ohta
Shin-Ichi
S
Sonoda
Akinaga
A
Yamada
Masatoshi
M
Yamamoto
Masaya
M
Nitta
Norihisa
N
Murata
Kiyoshi
K
Tabata
Yasuhiko
Y
D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents; D003037:Cobalt Radioisotopes / Q000008:administration & dosage*; D003287:Contrast Media; D005079:Excipients; D037741:Fullerenes; D005682:Gadolinium / Q000008:administration & dosage* / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy; D004369:Pentetic Acid; D010778:Photochemotherapy; D011092:Polyethylene Glycols; D013481:Superoxides / Q000737:chemistry / Q000528:radiation effects
D002614:Chelating Agents; D003037:Cobalt Radioisotopes; D003287:Contrast Media; D005079:Excipients; D037741:Fullerenes; D013481:Superoxides; D011092:Polyethylene Glycols; D004369:Pentetic Acid; D005682:Gadolinium