A Novel Doxorubicin Prodrug with GRP78 Recognition and Nucleus-Targeting Ability for Safe and Effective Cancer Therapy,Molecular Pharmaceutics

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A Novel Doxorubicin Prodrug with GRP78 Recognition and Nucleus-Targeting Ability for Safe and Effective Cancer Therapy
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-12-15 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00830
Guo-Bin Ding _{1,

2} , Junqing Sun _{1,

2} , Peng Yang _{1,

2} , Binchun Li ₁ , Ying Gao ₃ , Zhuoyu Li _{1,

2,

3}

Affiliation

Glucose-regulated protein of 78 kDa (GRP78) has become an attractive and novel target for tumor therapy. Design and construction of powerful delivery systems that could efficiently transport doxorubicin (DOX) to a tumor-cell nucleus remains a formidable challenge for improving the tumor therapeutic index and mitigating side effects to normal tissues. Herein, a novel doxorubicin prodrug (NDP) with GRP78 recognition and nucleus-targeting ability was synthesized by a facile chemical route. NDP exhibited an enhanced antiproliferative activity against colorectal cancer cells and could efficiently enter the cell nucleus. Furthermore, it is inspiring to note that NDP displayed a much stronger inhibitory efficacy against the growth of colorectal cancer xenografts in nude mice than free DOX and showed superior in vivo safety. Together, the work provides a novel GRP78 and nucleus-targeting strategy, and the NDP holds great promise to be used as a potent and safe chemotherapeutic agent.

中文翻译：

具有GRP78识别和核靶向能力的新型阿霉素前药，可用于安全有效的癌症治疗。

78 kDa的葡萄糖调节蛋白（GRP78）已成为肿瘤治疗的有吸引力和新颖的靶标。可以有效地将阿霉素（DOX）转运至肿瘤细胞核的强大递送系统的设计和构建，对于改善肿瘤治疗指数和减轻对正常组织的副作用仍然是一项艰巨的挑战。本文中，通过一种简便的化学途径合成了具有GRP78识别和核靶向能力的新型阿霉素前药（NDP）。NDP对结直肠癌细胞表现出增强的抗增殖活性，可以有效进入细胞核。此外，令人鼓舞的是，NDP对裸鼠中结直肠癌异种移植物的生长显示出比游离DOX更好的抑制作用，并显示出优越的体内安全性。一起，

更新日期：2017-12-15

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