A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer

被引：226

作者：

Li, Fangfei ^{[1
]}

Lu, Jun ^{[1
]}

Liu, Jin ^{[2
]}

Liang, Chao ^{[1
,2
]}

Wang, Maolin ^{[3
]}

Wang, Luyao ^{[1
,2
]}

Li, Defang ^{[2
]}

Yao, Houzong ^{[1
]}

Zhang, Qiulong ^{[1
]}

Wen, Jia ^{[4
]}

Zhang, Zong-Kang ^{[5
]}

Li, Jie ^{[5
]}

Lv, Quanxia ^{[1
]}

He, Xiaojuan ^{[2
]}

Guo, Baosheng ^{[2
]}

Guan, Daogang ^{[3
]}

Yu, Yuanyuan ^{[2
]}

Dang, Lei ^{[1
]}

Wu, Xiaohao ^{[2
]}

Li, Yongshu ^{[2
]}

Chen, Guofen ^{[6
]}

Jiang, Feng ^{[1
]}

Sun, Shiguo ^{[4
]}

Zhang, Bao-Ting ^{[5
]}

Lu, Aiping ^{[1
,2
,3
]}

Zhang, Ge ^{[1
,2
,3
]}

机构：

[1] Hong Kong Baptist Univ, Sch Chinese Med, Inst Precis Med & Innovat Drug Discovery PMID, Hong Kong 999077, Hong Kong, Peoples R China

[2] Hong Kong Baptist Univ, Sch Chinese Med, Inst Adv Translat Med Bone & Joint Dis TMBJ, Hong Kong 999077, Hong Kong, Peoples R China

[3] Hong Kong Baptist Univ, Sch Chinese Med, Inst Integrated Bioinfomed & Translat Sci IBTS, Hong Kong 999077, Hong Kong, Peoples R China

[4] Northwest Agr & Forestry Univ, Coll Sci, Yangling 712100, Shaanxi, Peoples R China

[5] Chinese Univ Hong Kong, Fac Med, Sch Chinese Med, Hong Kong 999077, Hong Kong, Peoples R China

[6] Nanfang Hosp, Dept Orthopaed & Traumatol, Guangzhou 510515, Guangdong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

PHASE-II TRIAL; NAB-PACLITAXEL; DRUG-DELIVERY; AS1411; NANOPARTICLES; CHEMOTHERAPY; RECOGNITION; EFFICACY; FUSION; RNA;

D O I：

10.1038/s41467-017-01565-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.

引用

页数：14

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