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 Li; Guofen Chen; Feng Jiang; Shiguo Sun; Bao Ting Zhang; Aiping Lyu; Ge Zhang

doi:10.1038/s41467-017-01565-6

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 journal › Journal article › peer-review

219 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 language	English
Article number	1390
Number of pages	14
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01565-6
Publication status	Published - 9 Nov 2017

Scopus Subject Areas

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-017-01565-6

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Li, F., Lu, J., Liu, J., Liang, C., Wang, M., Wang, L., Li, D., Yao, H., Zhang, Q., Wen, J., Zhang, Z. K., Li, J., Lv, Q., He, X., Guo, B., Guan, D., Yu, Y., Dang, L., Wu, X., ... Zhang, G. (2017). A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer. Nature Communications, 8(1), Article 1390. https://doi.org/10.1038/s41467-017-01565-6

@article{cb64b3b186674a78addae1c54450fe95,

title = "A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer",

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.",

author = "Fangfei Li and Jun Lu and Jin Liu and Chao Liang and Maolin Wang and Luyao Wang and Defang Li and Houzong Yao and Qiulong Zhang and Jia Wen and Zhang, {Zong Kang} and Jie Li and Quanxia Lv and Xiaojuan He and Baosheng Guo and Daogang Guan and Yuanyuan Yu and Lei Dang and Xiaohao Wu and Yongshu Li and Guofen Chen and Feng Jiang and Shiguo Sun and Zhang, {Bao Ting} and Aiping Lyu and Ge Zhang",

note = "Funding Information: This study was supported by the Science and Technology Innovation Commission of Shenzhen Municipality Funds (JCYJ2016022921035 to G.Z. and JCYJ20170307161659648 to F.L.).",

year = "2017",

month = nov,

day = "9",

doi = "10.1038/s41467-017-01565-6",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Li, F, Lu, J, Liu, J, Liang, C, Wang, M, Wang, L, Li, D, Yao, H, Zhang, Q, Wen, J, Zhang, ZK, Li, J, Lv, Q, He, X, Guo, B, Guan, D, Yu, Y, Dang, L, Wu, X, Li, Y, Chen, G, Jiang, F, Sun, S, Zhang, BT, Lyu, A & Zhang, G 2017, 'A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer', Nature Communications, vol. 8, no. 1, 1390. https://doi.org/10.1038/s41467-017-01565-6

TY - JOUR

T1 - A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer

AU - Li, Fangfei

AU - Lu, Jun

AU - Liu, Jin

AU - Liang, Chao

AU - Wang, Maolin

AU - Wang, Luyao

AU - Li, Defang

AU - Yao, Houzong

AU - Zhang, Qiulong

AU - Wen, Jia

AU - Zhang, Zong Kang

AU - Li, Jie

AU - Lv, Quanxia

AU - He, Xiaojuan

AU - Guo, Baosheng

AU - Guan, Daogang

AU - Yu, Yuanyuan

AU - Dang, Lei

AU - Wu, Xiaohao

AU - Li, Yongshu

AU - Chen, Guofen

AU - Jiang, Feng

AU - Sun, Shiguo

AU - Zhang, Bao Ting

AU - Lyu, Aiping

AU - Zhang, Ge

N1 - Funding Information: This study was supported by the Science and Technology Innovation Commission of Shenzhen Municipality Funds (JCYJ2016022921035 to G.Z. and JCYJ20170307161659648 to F.L.).

PY - 2017/11/9

Y1 - 2017/11/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85033787524&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-01565-6

DO - 10.1038/s41467-017-01565-6

M3 - Journal article

C2 - 29123088

AN - SCOPUS:85033787524

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1390

ER -

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

Abstract

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