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Surface‐functionalized nanoparticles for targeted gene delivery across nasal respiratory epithelium
Author(s) -
Sundaram Sneha,
Roy Shyamal K,
Ambati Balamurali K,
Kompella Uday B.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-129825
Subject(s) - plga , transferrin , lncap , biophysics , transfection , chemistry , nanoparticle , microbiology and biotechnology , nanotechnology , materials science , in vitro , cancer cell , biochemistry , medicine , biology , cancer , gene
The objective of this study was to determine whether surface‐modified nanoparticles enhance permeability across nasal mucosa, while retaining the effectiveness of the payload. The uptake and permeability of polystyrene nanoparticles (PS‐NPs;Fluo‐Spheres) was evaluated across the various regions of the bovine nasal epithelia following conjugation with deslorelin and transferrin. Uptake and transport of PS‐NPs, deslorelin‐PS‐NPs, and transferrin‐PS‐NPs exhibited regional differences in the order: inferior turbinate posterior (ITP) > medium turbinate posterior (MTP) > medium turbinate anterior (MTA). Uptake and transport also exhibited directionality and temperature dependence in these tissues. Further, uptake as well as transport of functionalized nanoparticles could be inhibited by excess free functionalizing ligand. Confocal microscopy indicated the presence of func‐tionalized nanoparticles in respiratory epithelial cells, as well as other cell types of the nasal tissue. We chose the ITP region for further studies with deslorelin or transferrin‐conjugated poly ‐L ‐lactide‐co‐glycolide nanoparticles (PLGA‐NPs) encapsulating an anti‐VEGF in‐traceptor (Flt23k) plasmid. Transport of the nanopar‐ticles, as well as the plasmid from the nanoparticles, exhibited the following order: transferrin‐PLGA‐NPs > deslorelin‐PLGA‐NPs > PLGA‐NPs ≫ plasmid. The ability of the nanoparticles transported across the nasal tissue to retain the effectiveness of the Flt23k plasmid was evaluated by measuring transfection efficiency (percentage of cells expressing GFP) and VEGF inhibition in LNCaP and PC‐3 prostate cancer cells. Transfection efficiencies and VEGF inhibition in LNCaP and PC‐3 cells exhibited the following trend: transferrin‐PLGA‐NPs ≥ deslorelin‐PLGA‐NPs > PLGA‐NPs ≫ plasmid. Further, functionalized nanoparticles exhibited transfection efficiencies and VEGF inhibition significantly superior compared with the routinely used transfecting agent, lipofectamine. Formulating plas‐mids into nanoparticulate delivery systems enhances the transnasal delivery and gene therapy at remote target cancer cells, which can be further enhanced by nanopar‐ticle functionalization with deslorelin or transferrin.— Sundaram, S., Roy, S. K., Ambati, B. K., Kompella, U. B. Surface functionalized nanoparticles for targeted gene delivery across nasal respiratory epithelium. FASEBJ. 23, 3752‐3765 (2009). www.fasebj.org