title: The anti-tumor efficacy of 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX): a novel paclitaxel bioreductive prodrug.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Duan
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Yin
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Shu-Shi
authors.initials: SS
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011422:Propionates / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072258:Tumor Hypoxia / Q000187:drug effects*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: C000625867:3-(2-nitrophenyl)propionic acid-paclitaxel; D000972:Antineoplastic Agents, Phytogenic; D010666:Phenylpropionates; D011355:Prodrugs; D011422:Propionates; D017239:Paclitaxel
keywords: 3-(2-Nitrophenyl) propionic acid; anti-tumor efficacy; bioreductive prodrug; paclitaxel; tumor hypoxia