Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy

• Published in: ACS nano 2015-06, Vol.9 (6), p.5913-5921
• Main Authors: Mi, Peng, Dewi, Novriana, Yanagie, Hironobu, Kokuryo, Daisuke, Suzuki, Minoru, Sakurai, Yoshinori, Li, Yanmin, Aoki, Ichio, Ono, Koji, Takahashi, Hiroyuki, Cabral, Horacio, Nishiyama, Nobuhiro, Kataoka, Kazunori
• Format: Article
• Language: English
• Subjects: Animals; Calcium Phosphates - chemistry; Cell Line, Tumor; Cell Proliferation; Chelating Agents; Contrast Media; Gadolinium DTPA; Humans; Magnetic Resonance Imaging - methods; Mice; Mice, Inbred BALB C; Micelles; Molecular Imaging; Neoplasms - diagnosis; Neoplasms - radiotherapy; Neutron Capture Therapy; Polymers - chemistry
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.5b00532

Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.