SapC-DOPS nanovesicles as targeted therapy for lung cancer.
SapC-DOPS nanovesicles as targeted therapy for lung cancer.
复制标题
SapC-DOPS 纳米囊泡作为肺癌的靶向治疗。
DOI：
10.1158/1535-7163.mct-14-0661
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发表时间：
2015
影响因子：
5.7
通讯作者：
Qi,Xiaoyang
中科院分区：
文献类型：
--
作者：
Zhao,Shuli;Chu,Zhengtao;Blanco,VictorM;Nie,Yunzhong;Hou,Yayi;Qi,Xiaoyang
肺癌是男性和女性最致命的癌症类型。在这项研究中，我们评估了由溶酶体蛋白（Saposin C，SapC）和磷脂（二油酰磷脂酰丝氨酸，DOPS）组成的生物制剂的体外和体内功效，其可以组装成具有选择性抗肿瘤活性的纳米囊泡（SapC-DOPS）。SapC-DOPS靶向磷脂酰丝氨酸，一种优先暴露在癌细胞和肿瘤相关血管系统表面的阴离子磷脂。因为SapC与磷脂酰丝氨酸的结合在酸性pH下是有利的，并且后者表征了许多实体瘤的环境，所以我们测试了pH对SapC-DOPS与肺肿瘤细胞的结合能力的影响。结果表明，SapC-DOPS在低pH值下与癌细胞的结合更加明显。对一组人肺肿瘤细胞的活力测定表明，SapC-DOPS的细胞毒性与细胞表面磷脂酰丝氨酸水平正相关，而线粒体膜电位测量结果与细胞凋亡相关的细胞死亡一致。在活体小鼠中使用荧光跟踪方法，我们表明SapC-DOPS特异性靶向人肺癌异种移植物，并且用SapC-DOPS的全身治疗诱导肿瘤细胞凋亡并显著抑制肿瘤生长。这些结果表明，SapC-DOPS纳米囊泡是肺癌的有希望的治疗选择（Mol Cancer Ther; 14（2）; 491-8）。©2015 AACR.
Lung cancer is the deadliest type of cancer for both men and women. In this study, we evaluate thein vitroandin vivoefficacy of a biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS), which can be assembled into nanovesicles (SapC–DOPS) with selective antitumor activity. SapC–DOPS targets phosphatidylserine, an anionic phospholipid preferentially exposed in the surface of cancer cells and tumor-associated vasculature. Because binding of SapC to phosphatidylserine is favored at acidic pHs, and the latter characterizes the milieu of many solid tumors, we tested the effect of pH on the binding capacity of SapC–DOPS to lung tumor cells. Results showed that SapC–DOPS binding to cancer cells was more pronounced at low pH. Viability assays on a panel of human lung tumor cells showed that SapC–DOPS cytotoxicity was positively correlated with cell surface phosphatidylserine levels, whereas mitochondrial membrane potential measurements were consistent with apoptosis-related cell death. Using a fluorescence tracking method in live mice, we show that SapC–DOPS specifically targets human lung cancer xenografts, and that systemic therapy with SapC–DOPS induces tumor apoptosis and significantly inhibits tumor growth. These results suggest that SapC–DOPS nanovesicles are a promising treatment option for lung cancer.Mol Cancer Ther; 14(2); 491–8. ©2015 AACR.