Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy.
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.
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Tao
T
Liu
Department of Pharmacology, Jiangxi Institute of Materia Medica, Nanchang, 330029, China.
Xidong
X
Wu
School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
Yigang
Y
Wang
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Tao
T
Zhang
Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan, 528041, China.
Ting
T
Wu
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Fang
F
Liu
Medical College of Nanchang University, Nanchang, 330038, China.
Wansong
W
Wang
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Gang
G
Jiang
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Minqiang
M
Xie
D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D020780:Matrix Metalloproteinase 9 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D011107:Polylysine / Q000737:chemistry; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage*; D014018:Tissue Distribution; D014162:Transfection; D047392:beta-Cyclodextrins / Q000737:chemistry
D008823:Micelles; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D043823:Taxoids; D047392:beta-Cyclodextrins; D000077143:Docetaxel; D011107:Polylysine; D005492:Folic Acid; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C031215:betadex
co-delivery; star-shaped; target