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
Autor: | Shuang Zhang, Jing-Ru Wang, Yan-Li Hao, Zhan-Tao Li, Xiao-Chuan Duan, Xin Yao, Mei-Qi Xu, Xuan Zhang, Xiu-Chai Zheng, Zhen-Han Feng, Man Liu, Hui Li, Zhuo-Yue Li |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Pharmaceutical Science Nanoparticle Apoptosis 02 engineering and technology Pharmacology bioreductive prodrug Mice chemistry.chemical_compound International Journal of Nanomedicine Drug Discovery Tumor Cells Cultured Prodrugs Original Research Mda mb 231 Antitumor activity Mice Inbred BALB C Mice Inbred ICR Phenylpropionates in vitro General Medicine Prodrug 021001 nanoscience & nanotechnology 3-(2-nitrophenyl) propionic acid-paclitaxel in vivo Paclitaxel Female 0210 nano-technology endocrine system Biophysics Mice Nude Breast Neoplasms Bioengineering In Vitro Techniques complex mixtures Biomaterials 03 medical and health sciences In vivo Animals Humans Distribution (pharmacology) antitumor activity Cell Proliferation Organic Chemistry technology industry and agriculture Xenograft Model Antitumor Assays In vitro 030104 developmental biology chemistry Nanoparticles |
Zdroj: | International Journal of Nanomedicine |
ISSN: | 1178-2013 |
Popis: | 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 |
Databáze: | OpenAIRE |
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