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Etoposide loaded layered double hydroxide nanoparticles reversing chemoresistance and eradicating human glioma stem cells in vitro and in vivo

Abstract

Glioblastoma (GBM) is the most malignant and lethal glioma in human brain tumors and contains self-renewing, tumorigenic glioma stem cells (GSCs) that contribute to tumor initiation, therapeutic resistance and further recurrence. In this study, we combined in vitro cellular efficacy with in vivo antitumor performance to evaluate the outcome of etoposide (VP16) loaded layered double hydroxide (LDH)nanocomposite (L-V) on human GSCs. The effects on GSCs proliferation and apoptosis showed that loaded with LDH could significantly sensitize GSCs to VP16 and enhance the GSCs elimination. Further qPCR and Western blot assays demonstrated that L-V could effectively attenuate GSCs related pluripotency gene expression and reduce the cancer stemness. In vivo GSCs xenograft mice model showed that L-V turned to overcome drug resistance, eradicate GSCs, sharply decrease the stemness and reverse the epithelial-mesenchymal transition (EMT). RNA-seq analysis elucidated that L-V play a vital role through down-regulating PI3K/AKt/mTOR expression, activating Wnt/GSK3β/β-catenin signaling pathway, hence leading to GSC stemness loss and greatly enhanced GSCs targeting effect. Taken together, this study demonstrated the outstanding performance of L-V reversing drug resistance of GSCs, thus providing a novel strategy for clinical translation application of nanomedicne in malignant gioma chemotherapy.

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Publication details

The article was received on 04 Apr 2018, accepted on 06 Jun 2018 and first published on 06 Jun 2018


Article type: Paper
DOI: 10.1039/C8NR02708K
Citation: Nanoscale, 2018, Accepted Manuscript
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    Etoposide loaded layered double hydroxide nanoparticles reversing chemoresistance and eradicating human glioma stem cells in vitro and in vivo

    Z. Wang, P. Liang, X. He, B. Wu, Q. Liu, Z. Xu, H. Wu, Z. Liu, Y. qian, S. Wang and R. Zhu, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR02708K

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