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Sustained cytoplasmic delivery and anti-viral effect of PLGA nanoparticles carrying a nucleic acid-hydrolyzing monoclonal antibody

Joung, YK; Son, S; Jang, JY; Kwon, MH; Park, KD
Pharmaceutical research, 29(4):932-942, 2012
Journal Title
Pharmaceutical research
PURPOSE: Cytoplasmic delivery of a monoclonal antibody (mAb) with nucleic acid-hydrolyzing activity (3D8 scFv) using poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated for persistent anti-viral effect.

METHODS: 3D8 scFv-loaded PLGA (3D8-PLGA) NPs were prepared via a double emulsion method that was previously optimized. Flow cytometry and confocal microscopy was carried out to confirm the cellular uptake and cytoplasmic localization. immunochemical and fluorescence resonance energy transfer (FRET) assays tested the cytoplasmic release and hydrolyzing effect of 3D8 scFv, respectively. Anti-viral activity test was performed using MTT assay with vesicular stomatitis virus (VSV)-infected HeLa cells.

RESULTS: 3D8-PLGA NPs were much more effectively taken into cells in dose- and time-dependent manner and localized in the cytosolic region, compared to free 3D8 scFv. 3D8 scFv was released and hydrolyzed RNAs in the cytoplasm, exhibiting the maxima at a period of time (12-24 h). Anti-viral activity test revealed that 3D8-PLGA NP has dose- and time-dependent anti-viral effect and the maximum effect at the dose of 2 mg/ml and the incubation of 3 days.

CONCLUSIONS: Cytoplasmic delivery of 3D8 scFv via PLGA NPs could enhance the viability of infected cells in sustained manner due to preserved activity, much improved cellular uptake and sustained release.
MeSH terms
AnimalsAntibodies, Monoclonal/*administration & dosage/chemistryAntiviral Agents/*administration & dosage/chemistryCell Line, TumorCell Survival/drug effectsCytosol/*metabolismDelayed-Action PreparationsDrug Carriers/administration & dosage/chemistryDrug Delivery Systems/methodsEmulsions/administration & dosage/chemistryHCT116 CellsHeLa CellsHumansHydrolysisLactic Acid/*administration & dosage/chemistryMiceNanoparticles/*administration & dosage/chemistryNucleic Acids/*metabolismPolyglycolic Acid/*administration & dosage/chemistryRNA/metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
권, 명희
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