Oncotarget

Research Papers:

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Tao Liu, Xidong Wu, Yigang Wang, Tao Zhang, Ting Wu, Fang Liu, Wansong Wang, Gang Jiang and Minqiang Xie _

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Oncotarget. 2016; 7:42017-42030. https://doi.org/10.18632/oncotarget.9771

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Abstract

Tao Liu1, Xidong Wu2, Yigang Wang3, Tao Zhang1, Ting Wu4, Fang Liu1, Wansong Wang5, Gang Jiang1, Minqiang Xie1

1Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

2Department of Pharmacology, Jiangxi Institute of Materia Medica, Nanchang, 330029, China

3School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, China

4Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan, 528041, China

5Medical College of Nanchang University, Nanchang, 330038, China

Correspondence to:

Tao Liu, email: taoliu18@126.com

Minqiang Xie, email: min_qiang_x@hotmail.com

Keywords: target, star-shaped, co-delivery

Received: March 18, 2016     Accepted: May 16, 2016     Published: June 01, 2016

ABSTRACT

The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.


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