Targeted cytosolic delivery of hydrogel nanoparticles into HepG2 cells through engineered Sendai viral envelopes.
Hydrogel nanoparticles of cross-linked polyvinylpyrrolidone (PVP-NP) (35-50 nm in diameter) containing fluoresceinated dextran (FITC-Dx) were encapsulated in reconstituted Sendai viral envelopes containing only the fusion (F) protein (F-virosomes(1)). Incubation of these loaded F-virosomes with human hepatoblastoma cells (HepG2) in culture resulted in membrane-fusion-mediated delivery of NPs to the cell cytoplasm, as inferred from the ability of cells to internalize FITC-Dx loaded PVP-NP (PVP(f)-NP) in the presence of azide (an inhibitor of the endocytotic process). Introduction of PVP(f)-NP into the HepG2 cells was assured by selective accumulation of FITC fluorescence in the cytosolic compartment. The structural integrity of the internalized PVP(f)-NP was also confirmed by fluorescence microscopy and ultracentrifugation analysis. The potential usefulness of PVP-NP-mediated cytosolic release of water soluble drugs both in vitro and in vivo has been established for the first time.
Jana
Siddhartha S
SS
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, 110021, New Delhi, India.
Bharali
Dhruba J
DJ
Mani
Prashant
P
Maitra
Amarnath
A
Gupta
Chhitar M
CM
Sarkar
Debi P
DP
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D008856:Microscopy, Fluorescence; D010316:Particle Size; D011205:Povidone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D029082:Sendai virus / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D020100:Hydrogels; D014760:Viral Fusion Proteins; C015219:fluorescein isothiocyanate dextran; D011205:Povidone; D016650:Fluorescein-5-isothiocyanate