Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo
Xiaoying Lei,1,* Ke Li,2,3,* Yan Liu,4,* Zhen Yu Wang,1 Ban Jun Ruan,1 Li Wang,1 An Xiang,1 Daocheng Wu,3 Zifan Lu1 1State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, The Fourth Military Medical University, 2Shaanxi Key Laboratory of Ischemic Cardiovascular...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/61fee79670984883894486614c1ec515 |
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| Sumario: | Xiaoying Lei,1,* Ke Li,2,3,* Yan Liu,4,* Zhen Yu Wang,1 Ban Jun Ruan,1 Li Wang,1 An Xiang,1 Daocheng Wu,3 Zifan Lu1 1State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, The Fourth Military Medical University, 2Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, Shaanxi, 3Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 4Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, Jilin, People’s Republic of China *These authors contributed equally to this work Abstract: A combination administration of chemical agents was highlighted to treat tumors. Recently, tumor cell has been found to be different from normal cell in metabolic manner. Most of cancer cells prefer aerobic glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) to satisfy energy and biomass synthesis requirement to survive, grow and proliferate, which provides novel and potential therapeutic targets for chemotherapy. Here, 2-deoxy-d-glucose (2-DG), a potent inhibitor of glucose metabolism, was used to inhibit glycolysis of tumor cells; α-tocopheryl succinate (α-TOS), a water-insoluble vitamin E derivative, was chosen to suppress OXPHOS. Our data demonstrated that the combination treatment of 2-DG and α-TOS could significantly promote the anti-tumor efficiency in vitro compared with administration of the single drug. In order to maximize therapeutic activity and minimize negative side effects, a co-delivery nanocarrier targeting folate receptor (FR) was developed to encapsulate 2-DG and α-TOS simultaneously based on our previous work. Transmission electron microscope, dynamic light scattering method and UV-visible spectrophotometers were used to investigate morphology, size distribution and loading efficiency of the α-TOS-2-DG-loaded and FR-targeted nanoparticles (TDF NPs). The TDF NPs were found to possess a layer-by-layer shape, and the dynamic size was <100 nm. The final encapsulation efficiencies of α-TOS and 2-DG in TDF NPs were 94.3%±1.3% and 61.7%±7.7% with respect to drug-loading capacities of 8.9%±0.8% and 13.2%±2.6%, respectively. Almost no α-TOS release was found within 80 h, and release of 2-DG was sustained and slow within 72 h. The results of FR binding assay and fluorescence biodistribution revealed that TDF NPs could target FR highly expressed on tumor cell in vitro and in vivo. Further, in vivo anti-tumor experiments showed that TDF NPs had an improved biological function with less toxicity. Thus, our work indicates that the co-delivery TDF NPs have a great potential in tumor therapy. Keywords: co-delivery nanocarrier, α-tocopheryl succinate, 2-deoxyglucose, anti-tumor |
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