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
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