Research Papers:

The anti-tumor efficacy of 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX): a novel paclitaxel bioreductive prodrug

Ping Song, Xin Yao, Ting Zhong, Shuang Zhang, Yang Guo, Wei Ren, Dan Huang, Xiao-Chuan Duan, Yi-Fan Yin, Shu-Shi Zhang and Xuan Zhang _

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Oncotarget. 2016; 7:48467-48480. https://doi.org/10.18632/oncotarget.10310

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Ping Song2,*, Xin Yao1,2,*, Ting Zhong1,2, Shuang Zhang1,2, Yang Guo1,2, Wei Ren1,2, Dan Huang1,2, Xiao-Chuan Duan1,2, Yi-Fan Yin1, Shu-Shi Zhang1, Xuan Zhang1,2

1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

*These authors have contributed equally to this work

Correspondence to:

Xuan Zhang, email: [email protected]

Keywords: paclitaxel, 3-(2-Nitrophenyl) propionic acid, bioreductive prodrug, tumor hypoxia, anti-tumor efficacy

Received: February 15, 2016    Accepted: June 09, 2016    Published: June 27, 2016


Hypoxia is an important microenvironmental pressure present in the majority of solid tumors and, so, tumor hypoxia might be considered an attractive target for tumor therapy. One strategy for targeting hypoxia is to develop bioreductive prodrugs. In the present research, we synthesized a bioreductive paclitaxel prodrug, 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX). The stability of NPPA-PTX in PBS and rat plasma was investigated. The anti-tumor activity of NPPA-PTX was also evaluated in vitro and in vivo. The results of our stability study indicated that NPPA-PTX was stable in PBS and rat plasma as well as in the blood circulation. The in vitro and in vivo anti-tumor activity of NPPA-PTX was confirmed in both KB cells and MDA-MB-231 cells. Our results also indicated that NPPA-PTX could completely convert to active PTX in tumor tissues and produced the anti-tumor activity in both KB and MDA-MB-231 tumor-bearing nude mice. We suggest that the dissociated PTX which converted from NPPA-PTX in tumor tissues played a key role in producing anti-tumor activity. Considering all our results, we suggest that NPPA-PTX is a novel bioreductive PTX prodrug which could undergo further evaluation.

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