An RGD-modified MRI-visible polymeric vector for targeted siRNA delivery to hepatocellular carcinoma in nude mice.
RNA interference (RNAi) has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC). Targeted vectors are able to deliver small interfering RNA (siRNA) into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD)-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION), was constructed as a magnetic resonance imaging (MRI)-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe.
Molecular Imaging Lab, Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Chun
C
Wu
Faming
F
Gong
Pengfei
P
Pang
Min
M
Shen
Kangshun
K
Zhu
Du
D
Cheng
Zhihao
Z
Liu
Hong
H
Shan
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D058185:Magnetite Nanoparticles; C507107:PEI-g-PEG-RGD; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D000077022:Survivin; D011092:Polyethylene Glycols