Sustained cytoplasmic delivery and anti-viral effect of PLGA nanoparticles carrying a nucleic acid-hydrolyzing monoclonal antibody
- Sustained cytoplasmic delivery and anti-viral effect of PLGA nanoparticles carrying a nucleic acid-hydrolyzing monoclonal antibody
- 정윤기; 손세진; 장지영; 권명희; 박기동
- antiviral effect; cytoplasmic delivery; drug
delivery; monoclonal antibody; nanoparticles
- Issue Date
- Pharmaceutical research
- VOL 29, NO 4, 932-924
- Purpose Cytoplasmic delivery of a monoclonal antibody (mAb)
with nucleic acid-hydrolyzing activity (3D8 scFv) using poly(lacticco-
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
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