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

Fangfei LI, Jun Lu, Jin LIU, Chao LIANG, Maolin Wang, Luyao Wang, Defang LI, Houzong Yao, Qiulong Zhang, Jia Wen, Zong Kang Zhang, Jie Li, Quanxia Lv, Xiaojuan He, Baosheng GUO, Daogang GUAN, Yuanyuan YU, Lei Dang, Xiaohao Wu, Yongshu LiGuofen Chen, Feng Jiang, Shiguo Sun, Bao Ting Zhang*, Aiping LYU, Ge ZHANG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1390
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Scopus Subject Areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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