Nucleolin-targeting liposomes guided by aptamer AS1411 for the delivery of siRNA for the treatment of malignant melanomas.
BRAF gene mutation is found in more than 60% of malignant melanomas, which are difficult to treat. In this study, a new tumor-targeting liposome was developed to deliver anti-BRAF siRNA (siBraf) for the treatment of melanomas. Nucleolin is overexpressed on the surface of cancer cells. AS1411, an aptamer showing specific binding to nucleolin, was conjugated to PEGylated cationic liposome as the targeting probe ASLP (AS1411-PEG-liposome). The ASLP/siRNA complex was formed through electrostatic interaction between ASLP and siRNA. The binding of AS1411 to the surface of PEGylated liposomes was confirmed by gel electrophoresis and capillary electrophoresis. Real-time PCR and Western blot analysis showed that ASLP/siBraf exhibited strong silencing activity of BRAF gene. The much higher accumulation of the siRNA in tumor cells comparing with normal cells indicated that ASLP displayed excellent tumor-targeting capability. Notably, ASLP/siBraf showed significant silencing activity in A375 tumor xenograft mice and inhibited the melanoma growth. These results suggested that the new nucleolin-targeted siRNA delivery system by AS1411 may have the potential for the treatment of melanoma.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Liyu
L
Li
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Jianjun
J
Hou
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xinjie
X
Liu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yujia
Y
Guo
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: wuyun_sioc@hotmail.com.
Yun
Y
Wu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Lihe
L
Zhang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: yangzj@bjmu.edu.cn.
Zhenjun
Z
Yang
D052157:Aptamers, Nucleotide; D015153:Blotting, Western; D004337:Drug Carriers; D019075:Electrophoresis, Capillary; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008081:Liposomes; D008545:Melanoma / Q000188:drug therapy*; D046529:Microscopy, Electron, Transmission; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016601:RNA-Binding Proteins / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000188:drug therapy*; D000097796:Nucleolin
D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100
Liposomes; Melanomas; Nucleolin AS1411; Therapeutic effect; siRNA delivery