International Journal of Nanomedicine (Dec 2018)

Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo

  • Duan X,
  • Yao X,
  • Zhang S,
  • Xu M,
  • Hao Y,
  • Li Z,
  • Zheng X,
  • Liu M,
  • Li Z,
  • Li H,
  • Wang J,
  • Feng Z,
  • Zhang X

Journal volume & issue
Vol. Volume 14
pp. 195 – 204

Abstract

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Xiao-Chuan Duan,1,2,* Xin Yao,1,2,* Shuang Zhang,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Xiu-Chai Zheng,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Hui Li,1 Jing-Ru Wang,1,2 Zhen-Han Feng,1 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China *These authors contributed equally to this work Background: 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX) is a paclitaxel (PTX) bioreductive prodrug synthesized by our lab. We hypothesize that NPPA-PTX can self-assemble to form nanoparticles (NPs). Materials and methods: In the present research, the theoretical partition coefficient (XlogP) and Hansen solubility parameters of NPPA-PTX were calculated. NPPA-PTX nanoparticles prepared by NPPA-PTX and DSPE-PEG (NPPA-PTX:DSPE-PEG =1:0.1, w/w) (NPPA-PTX@PEG NPs) were prepared and characterized. The cellular uptake, in vitro antitumor activity, in vivo targeting effect, tumor distribution, in vivo antitumor activity, and safety of NPPA-PTX@PEG NPs were investigated. Results: Our results indicate that NPPA-PTX can self-assemble to form NPPA-PTX@PEG NPs. Both the cellular uptake and safety of NPPA-PTX@PEG NPs were higher than those of Taxol. NPPA-PTX@PEG NPs could target tumor tissues by a passive targeting effect. In tumor tissues, NPPA-PTX@PEG NPs could completely transform into active PTX. The in vivo antitumor activity of NPPA-PTX@PEG NPs was confirmed in MDA-MB-231 tumor-bearing nude mice. Conclusion: The bioreductive prodrug NPPA-PTX could self-assemble to form NPs. The safety and antitumor activity of NPPA-PTX@PEG were confirmed in our in vitro and in vivo experiments. The NPPA-PTX@PEG NPs developed in this study could offer a new way of preparing bioreductive prodrug, self-assembled NPs suitable for antitumor therapy. Keywords: bioreductive prodrug, 3-(2-nitrophenyl) propionic acid-paclitaxel, nanoparticles, antitumor activity, in vitro, in vivo

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