title: A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour effects.
abstract: Tumour targeting nanotechnology has recently made therapeutic progress and several therapeutic nanoparticles have been approved for clinical application. However, an ideal nanotechnology based therapeutic for solid tumours, particularly for systemic administration, still remains a challenge in clinical cancer therapy. We previously reported a pH sensitive in vivo delivery system of doxorubicin, or microRNA, using carbonate apatite (CA) nanoparticles. To further explore utility of CA in cancer therapy, we attempted to transport excess glucose into tumour cells by conjugating glucose (Glc) to the nanoparticle. Despite the non-toxicity of CA and Glc, the complex (CA-[Glc]) exhibited an unexpected anti-cancer effect in vitro and in vivo. CA-[Glc] significantly reduced the growth of colon cancer cell lines. Intravenous injections successfully suppressed solid tumour growth. In mice and monkeys, intravenously injected CA-[Glc] complex resulted in no serious abnormalities in body weight or blood chemistry. Because cancer cells intensively metabolise glucose than normal cells, treatment of cancer using glucose seems paradoxical. However, with the aid of CA, this safe and 'sweet' complex may be a novel anti-cancer reagent.
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: 1] Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan [2] Research Fellow of Japan Society for the Promotion of Science.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Nakanishi Gastroenterological Research Institute, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Nakanishi Gastroenterological Research Institute, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Biomaterials Science, Graduate School of Dentistry, Osaka University, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sasaki
authors.affiliation: Department of Biomaterials Science, Graduate School of Dentistry, Osaka University, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imazato
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001031:Apatites / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001031:Apatites; D017382:Reactive Oxygen Species; C030782:carboapatite; D005947:Glucose