Synergistic combination chemotherapy using carrier-free celastrol and doxorubicin nanocrystals for overcoming drug resistance

作者: Yating Xiao , Jing Liu , Mengyu Guo , Huige Zhou , Jun Jin

DOI: 10.1039/C8NR02700E

关键词:

摘要: A key challenge of chemotherapy in clinical treatments is multidrug resistance (MDR), which mainly arises from drug efflux-induced tumor cell survival. Thus, it necessary to provide biocompatible chemotherapeutics improve accumulation MDR cells. Herein, two small molecular drugs, celastrol (CST) and doxorubicin (DOX), were self-assembled into carrier-free nanoparticles (CST/DOX NPs) via a simple green precipitation method for synergistic combination overcome DOX resistance. These spherical CST/DOX NPs can the water-solubility CST, reduce dosage DOX, therefore significantly enhance cellular by activating heat shock factor 1 (HSF-1) inhibiting NF-κB depress P-gp expression, results apoptosis autophagy resistant cells through ROS/JNK signaling pathway. Finally, was attained both MCF-7/MDR 3D multicellular spheroids. an alternative overcoming future applications.

参考文章(42)
Niravkumar R Patel, Bhawani Aryasomayajula, Abraham H Abouzeid, Vladimir P Torchilin, Cancer cell spheroids for screening of chemotherapeutics and drug-delivery systems Therapeutic Delivery. ,vol. 6, pp. 509- 520 ,(2015) , 10.4155/TDE.15.1
Bingbing Lin, Hongying Su, Rongrong Jin, Danyang Li, Changqiang Wu, Xin Jiang, Chunchao Xia, Qiyong Gong, Bin Song, Hua Ai, Multifunctional dextran micelles as drug delivery carriers and magnetic resonance imaging probes Science Bulletin. ,vol. 60, pp. 1272- 1280 ,(2015) , 10.1007/S11434-015-0840-X
Hua Zhang, Hongxiang Hu, Haoran Zhang, Wenbing Dai, Xinglin Wang, Xueqing Wang, Qiang Zhang, Effects of PEGylated paclitaxel nanocrystals on breast cancer and its lung metastasis. Nanoscale. ,vol. 7, pp. 10790- 10800 ,(2015) , 10.1039/C4NR07450E
Suresh V Ambudkar, Chava Kimchi-Sarfaty, Zuben E Sauna, Michael M Gottesman, P-glycoprotein: from genomics to mechanism Oncogene. ,vol. 22, pp. 7468- 7485 ,(2003) , 10.1038/SJ.ONC.1206948
Antero Salminen, Marko Lehtonen, Tuomas Paimela, Kai Kaarniranta, Celastrol: Molecular targets of Thunder God Vine Biochemical and Biophysical Research Communications. ,vol. 394, pp. 439- 442 ,(2010) , 10.1016/J.BBRC.2010.03.050
Marina A. Dobrovolskaia, Scott E. McNeil, Immunological properties of engineered nanomaterials. Nature Nanotechnology. ,vol. 2, pp. 469- 478 ,(2007) , 10.1038/NNANO.2007.223
Giovambattista Pani, Tommaso Galeotti, Paola Chiarugi, Metastasis: cancer cell’s escape from oxidative stress Cancer and Metastasis Reviews. ,vol. 29, pp. 351- 378 ,(2010) , 10.1007/S10555-010-9225-4
Min Li-Weber, Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Letters. ,vol. 332, pp. 304- 312 ,(2013) , 10.1016/J.CANLET.2010.07.015
K. Krishnamurthy, K. Vedam, R. Kanagasabai, L. J. Druhan, G. Ilangovan, Heat shock factor-1 knockout induces multidrug resistance gene, MDR1b, and enhances P-glycoprotein (ABCB1)-based drug extrusion in the heart Proceedings of the National Academy of Sciences of the United States of America. ,vol. 109, pp. 9023- 9028 ,(2012) , 10.1073/PNAS.1200731109
Zibin Gao, Linan Zhang, Yongjun Sun, Nanotechnology applied to overcome tumor drug resistance Journal of Controlled Release. ,vol. 162, pp. 45- 55 ,(2012) , 10.1016/J.JCONREL.2012.05.051