Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy

• DOI: 10.1016/j.jconrel.2006.10.008
• Publication Date: 2006-10-11T11:37:56Z
• Authors: Jian Liu; Shin-ichi Ohta; Akinaga Sonoda; Masatoshi Yamada; Masaya Yamamoto; Norihisa Nitta; Kiyoshi Murata; Yasuhiko Tabata
• Keywords: diagnoses; 0301 basic medicine; fullerene; Contrast Media; Gadolinium; Pentetic Acid; Magnetic Resonance Imaging; Polyethylene Glycols; Excipients; Mice; 03 medical and health sciences; photodynamic therapy; Photochemotherapy; Superoxides; Cell Line, Tumor; Neoplasms; Injections, Intravenous; Animals; Fullerenes; Cobalt Radioisotopes; Neoplasm Transplantation; MRI; antitumor; Chelating Agents

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.