Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive chemodrugs

Shan Liu; Dilong Chen; Yuming Yuan; Xue Zhang; Yao Li; Shenglei Yan; Jingqing Zhang

doi:10.18632/oncotarget.17536

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Research Papers:

Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive chemodrugs

Shan Liu, Dilong Chen, Yuming Yuan, Xue Zhang, Yao Li, Shenglei Yan and Jingqing Zhang _

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Oncotarget. 2017; 8:65042-65055. https://doi.org/10.18632/oncotarget.17536

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Abstract

Shan Liu1,*, Dilong Chen2,*, Yuming Yuan1,*, Xue Zhang1,*, Yao Li1,*, Shenglei Yan1 and Jingqing Zhang1

1Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China

2Tumor Drug Engineering Research Center, Chongqing Three Gorges Medical College, Chongqing 404120, China

*These authors contributed equally to this work

Correspondence to:

Jingqing Zhang, email: [email protected]

Keywords: efficient delivery, cancer cells, nanoemulsive chemodrugs, improved bioavailability, in situ absorption characteristics

Received: February 24, 2017 Accepted: April 15, 2017 Published: April 28, 2017

ABSTRACT

Evodiamine has been documented to possess activities in numerous cancer cells. Our preliminary study showed that A549 cells were insensitive to evodiamine. In this paper, A549 cells are sensitive to nanoemulsive evodiamine (EVONE) through an efficient intracellular and systematic delivery. EVONE entered tumor cells by energy-dependent and mainly through clathrin-mediated endocytosis. EVONE exerted a higher cytotoxicity in a dose- and time-dependent manner. The enhanced induction of cell cycle arrest was ascribed to the down-regulation of cyclin B and cyclin dependent kinase 1, while the enhanced induction of apoptosis was due to the activation of caspase −3, −8 and −9 and the decreased B-cell lymphoma 2/ assaciated X protein ratio. Furthermore, the in vivo kinetic, bioavailability and in situ absorption characteristics of EVONE were much better than those of free evodiamine. The cancer cells insensitive to free chemodrugs became sensitive to nanoemulsive chemodrugs.

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Research Papers:

Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive chemodrugs

Abstract