An MRI-visible non-viral vector for targeted Bcl-2 siRNA delivery to neuroblastoma.
Polyethylene glycol-grafted polyethylenimine (PEG-g-PEI) which was functionalized with a neuroblastoma cell-specific ligand, the GD2 single chain antibody (scAb(GD2)), was synthesized in order to effectively deliver Bcl-2 siRNA into neuroblastoma cells. This polymer was complexed first with superparamagnetic iron oxide nanoparticle (SPION) to get a MRI-visible targeted non-viral vector (scAb(GD2)-PEG-g-PEI-SPION) and then with Bcl-2 siRNA to form nanoparticles showing low cytotoxicity. The targeting capacity of scAb(GD2)-PEG-g-PEI-SPION was successfully verified in vivo and in vitro by magnetic resonance imaging. The single chain antibody encoded targeted polyplex was more effective in transferring Bcl-2 siRNA than the nontargeting one in SK-N-SH cells, a human neuroblastoma cell line, resulting in a 46.34% inhibition in the expression of Bcl-2 mRNA. Consequently, a high level of cell apoptosis up to 50.76% and a significant suppression of tumor growth were achieved, which indicates that scAb(GD2)-PEG-g-PEI-SPION is a promising magnetic resonance imaging-visible non-viral vector for targeted neuroblastoma siRNA therapy and diagnosis.
Molecular Imaging Lab, Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Min
M
Shen
Faming
F
Gong
Pengfei
P
Pang
Kangshun
K
Zhu
Xiaochun
X
Meng
Chun
C
Wu
Jin
J
Wang
Hong
H
Shan
Xintao
X
Shuai
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005732:Gangliosides; D058185:Magnetite Nanoparticles; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D057127:Single-Chain Antibodies; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; C019403:ganglioside, GD2; D011094:Polyethyleneimine