A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour effects.
A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour effects.
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DOI：
10.1038/srep07742
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发表时间：
2015-01-13
影响因子：
4.6
通讯作者：
Mori M
中科院分区：
文献类型：
--
作者：
Yamamoto H;Wu X;Nakanishi H;Yamamoto Y;Uemura M;Hata T;Nishimura J;Takemasa I;Mizushima T;Sasaki J;Imazato S;Matsuura N;Doki Y;Mori M
近年来，肿瘤靶向纳米技术在治疗方面取得了进展，一些治疗性纳米颗粒已被批准用于临床应用。然而，一种理想的基于纳米技术的实体瘤治疗剂，特别是用于全身给药的治疗剂，仍然是临床癌症治疗中的挑战。我们先前报道了使用碳酸磷灰石（CA）纳米颗粒的多柔比星或microRNA的pH敏感的体内递送系统。为了进一步探索CA在癌症治疗中的效用，我们试图通过将葡萄糖（Glc）缀合到纳米颗粒来将过量的葡萄糖转运到肿瘤细胞中。尽管CA和Glc无毒性，但复合物（CA-[Glc]）在体外和体内表现出意想不到的抗癌作用。CA-[Glc]显著降低结肠癌细胞系的生长。静脉注射成功地抑制了实体瘤的生长。在小鼠和猴中，静脉注射CA-[Glc]复合物未导致体重或血液化学的严重异常。因为癌细胞比正常细胞强烈代谢葡萄糖，所以使用葡萄糖治疗癌症似乎是矛盾的。然而，在CA的帮助下，这种安全且“甜蜜”的配合物可能是一种新型的抗癌试剂。
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.