The Superior Antitumor Effect of Self-Assembled Paclitaxel Nanofilaments for Lung Cancer Cells
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Published:2018-12-14
Issue:2
Volume:16
Page:171-178
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ISSN:1567-2018
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Container-title:Current Drug Delivery
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language:en
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Short-container-title:CDD
Author:
He Mengyu1, Zhu Jiali1, Yu Na2, Kong Hui1, Zeng Xiaoning1, Xie Weiping1, Xu Huae1
Affiliation:
1. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China 2. Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China
Abstract
Objectives: Paclitaxel (Ptx) has been regarded as one of the most effective chemotherapeutic
drugs for lung cancers. Increasing studies focused on the nano-delivery system of Ptx due to its poor
solubility and hypersensitivity. The aim of the recent study was to investigate the antitumor effects of
self-assembled Ptx nano-filaments for lung cancer cells.
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Methods: In the present study, we designed and synthesized novel Ptx-loaded nano-filaments through
conjugation of Ptx and succinic acid (SA) (Ptx-SA, P-NFs). Non-small cell lung cancer (NSCLC) A549
and H460 cells were used for detecting the antitumor effects of P-NFs, including cytotoxicity, apoptosis,
and migration. Western blotting was performed for analyzing mechanism.
Results:
P-NFs nano-filaments exerted superior antitumor effects against NSCLC cells compared with
free Ptx using cytotoxicity tests. Furthermore, P-NFs nano-filaments were much more effective in inducing
NSCLC cells apoptosis and inhibiting A549 cells migration than free Ptx. To elucidate the underlying
mechanisms, the expression of apoptotic and endoplasmic reticulum (ER) stress proteins was
detected. The results indicated that P-NFs nano-filaments enhanced the expression of bax/bcl-2, protein
kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), phospho-
c-Jun N-terminal kinase (p-JNK), and C/EPB homologous protein (CHOP), which suggested that
the strong antitumor effect of P-NFs nano-filaments may be partially attributed to the activation ER
stress.
The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of
lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies
for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.
Funder
Jiangsu Province Major Scientific and Technological Special Project National Major Scientific and Technological Project for Significant New Drugs Development National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science
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