Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel.

Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel.
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DOI:
10.2217/nnm.14.194
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发表时间:
2015
期刊:
Nanomedicine (London, England)
影响因子:
--
通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
其他
文献类型:
--
作者:
Hanaoka H;Nakajima T;Sato K;Watanabe R;Phung Y;Gao W;Harada T;Kim I;Paik CH;Choyke PL;Ho M;Kobayashi H

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评价Glypican-3 (GPC3)靶向光免疫疗法(PIT)联合纳米颗粒白蛋白结合紫杉醇(nab-paclitaxel)治疗肝癌的疗效。表达A431/G1的GPC3细胞与酞菁衍生物IRDye700DX (IR700)一起孵育,该衍生物与抗GPC3抗体IR700- yp7偶联,并暴露于近红外光下。对A431/G1荷瘤小鼠进行gpc3靶向PIT联合nab-紫杉醇治疗实验。IR700-YP7结合A431/G1细胞,通过近红外光照射诱导体外快速靶向性坏死细胞死亡。IR700-YP7在A431/G1肿瘤中积累。与未处理的对照组相比,PIT抑制肿瘤生长。此外,PIT显著增加了纳紫杉醇的输送,提高了治疗效果。靶向GPC3的PIT联合nab-紫杉醇治疗肝癌是一种很有前景的治疗方法。
Effectiveness of Glypican-3 (GPC3)-targeted photoimmunotherapy (PIT) combined with the nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for hepatocellular carcinoma was evaluated. GPC3 expressing A431/G1 cells were incubated with a phthalocyanine-derivative, IRDye700DX (IR700), conjugated to an anti-GPC3 antibody, IR700-YP7 and exposed to near-infrared light. Therapeutic experiments combining GPC3-targeted PIT with nab-paclitaxel were performed in A431/G1 tumor-bearing mice. IR700-YP7 bound to A431/G1 cells and induced rapid target-specific necrotic cell death by near-infrared light exposure in vitro. IR700-YP7 accumulated in A431/G1 tumors. Tumor growth was inhibited by PIT compared with nontreated control. Additionally, PIT dramatically increased nabpaclitaxel delivery and enhanced the therapeutic effect. PIT targeting GPC3 combined with nab-paclitaxel is a promising method for treating hepatocellular carcinoma.