Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy
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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
Tao Liu, email: email@example.com
Minqiang Xie, email: firstname.lastname@example.org
Keywords: target, star-shaped, co-delivery
Received: March 18, 2016 Accepted: May 16, 2016 Published: June 01, 2016
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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