Abstract
An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFv(CD44v6),-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFv(CD44v6)-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFv(CD44v6)-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.
Keywords:
CD44 variant 6; magnetic resonance imaging; nonviral vector; small interfering RNA; tumor targeting.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Survival / drug effects
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Contrast Media / administration & dosage
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Contrast Media / chemistry
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Contrast Media / pharmacokinetics
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Drug Carriers / administration & dosage
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Drug Carriers / chemistry
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Drug Carriers / pharmacokinetics*
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Female
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Genetic Vectors / administration & dosage
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Genetic Vectors / chemistry
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Genetic Vectors / pharmacokinetics
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Histocytochemistry
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Humans
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Magnetic Resonance Imaging / methods*
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Mice
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Mice, Nude
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry*
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Polyethylene Glycols / administration & dosage
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Polyethylene Glycols / chemistry
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Polyethylene Glycols / pharmacokinetics
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Polyethyleneimine / administration & dosage
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Polyethyleneimine / analogs & derivatives
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Polyethyleneimine / chemistry
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Polyethyleneimine / pharmacokinetics
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RNA, Small Interfering / administration & dosage*
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RNA, Small Interfering / chemistry
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RNA, Small Interfering / pharmacokinetics*
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Single-Chain Antibodies / administration & dosage
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Single-Chain Antibodies / chemistry
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Single-Chain Antibodies / pharmacokinetics
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Stomach Neoplasms / genetics*
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Stomach Neoplasms / therapy*
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Transfection
Substances
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Contrast Media
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Drug Carriers
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RNA, Small Interfering
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Single-Chain Antibodies
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poly(ethylene glycol)-co-poly(ethyleneimine)
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Polyethylene Glycols
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Polyethyleneimine