Star-shaped cyclodextrin-poly(l-lysine) derivative co-delivering docetaxel and MMP-9 siRNA plasmid in cancer therapy.
A new cyclodextrin derivative (CD-PLLD) consisting of a β-cyclodextrin core and poly(l-lysine) dendron arms was prepared by the click conjugation of per-6-azido-b-cyclodextrin with propargyl focal point poly(l-lysine) dendron of third generation, and then used for docetaxel (DOC) and the best siRNA plasmid targeting MMP-9 (pMR3) co-delivery. Different from commonly used amphiphilic copolymers with cationic character, the as obtained cyclodextrin derivative may be used directly for the combinatorial delivery of nucleic acid and lipophilic anticancer drugs without a complicated micellization process. It was found that CD-PLLD/pMR3 nanocomplex showed a good gene transfection efficiency in vitro, and could mediate the reduce of MMP-9 protein in HNE-1 cells. For co-delivery analysis, the obtained CD-PLLD/DOC/pMR3 complexes could induce a more significant apoptosis than DOC or pMR3 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, which should be encouraged in nasopharyngeal cancer therapy.
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Tao
T
Liu
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Wei
W
Xue
Jiangxi Key Laboratory of Hematological Oncology and Cell Biology, Jiangxi Provincial People's Hospital, Nanchang 330006, China.
Bo
B
Ke
Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: min_qiang_x@hotmail.com.
Min-Qiang
MQ
Xie
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address: madong_jnu@163.com.
Dong
D
Ma
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001483:Base Sequence; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000737:chemistry*; D017931:DNA Primers; D000077143:Docetaxel; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010957:Plasmids; D011107:Polylysine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D003505:Cyclodextrins; D017931:DNA Primers; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D011107:Polylysine; D020780:Matrix Metalloproteinase 9
Co-delivery; Nasopharyngeal cancer; Poly(l-lysine) dendron arms; Star polymers