Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo

Xin Shuai Wang, Li Zhang, Xiaocen Li, De Jiu Kong, Xiao Chen Hu, Xue Zhen DIng, Jun Qiang Yang, Meng Qi Zhao, Yixuan He, Kit Lam, She Gan Gao, Tzu-Yin Lin, Yuanpei Li

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Aim: This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. Materials & methods: We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. Results: Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. Conclusion: The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.

Original languageEnglish (US)
Pages (from-to)1107-1120
Number of pages14
JournalNanomedicine
Volume13
Issue number10
DOIs
StatePublished - May 1 2018

Keywords

  • AZD9291
  • EGFR inhibitor
  • NSCLC
  • paclitaxel

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Development

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  • Cite this

    Wang, X. S., Zhang, L., Li, X., Kong, D. J., Hu, X. C., DIng, X. Z., Yang, J. Q., Zhao, M. Q., He, Y., Lam, K., Gao, S. G., Lin, T-Y., & Li, Y. (2018). Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo. Nanomedicine, 13(10), 1107-1120. https://doi.org/10.2217/nnm-2017-0355