Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells

Abstract

Background: Gene therapy is a potentially effective therapeutic modality for treating sensorineural hearing loss. Nonviral gene delivery vectors are expected to become extremely safe and convenient, and nanoparticles are the most promising types of vectors. However, infrequent nuclear localization in the cochlear cells limits their application for gene therapy. This study aimed to investigate the potential nuclear entry of hyperbranched polylysine nanoparticles (HPNPs) for gene delivery to cochlear targets. Methods: Rat primary cochlear cells and cochlear explants generated from newborn rats were treated with different concentrations of HPNPs. For the in vivo study, HPNPs were administered to the rats’ round window membranes. Subcellular distribution of HPNPs in different cell populations was observed with confocal microscope 24 hours after administration. Results: Nuclear entry was observed in various cochlear cell types in vitro and in vivo. In the primary cochlear cell culture, concentration-dependent internalization was observed. In the cochlear organotypic culture, abundant HPNPs were found in the modiolus, including the spiral ganglion, organ of Corti, and lateral wall tissues. In the in vivo study, a gradient distribution of HPNPs through different layers of the round window membrane was observed. HPNPs were also distributed in the cells of the middle ear tissue. Additionally, efficient internalization of HPNPs was observed in the organ of Corti and spiral ganglion cells. In primary cochlear cells, HPNPs induced higher transfection efficiency than did Lipofectamine ™ . Conclusion: These results suggest that HPNPs are potentially an ideal carrier for gene delivery into the cochlea.

Hyaluronan up-regulation is linked to renal dysfunction and hearing loss induced by silver nanoparticles

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Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

“…20 L929, a normal cell line, has been widely used in a series of studies including drug delivery to the inner ear. 21,22 As shown in Figure 1A, the viability of L929 cells remained high after being treated with the four types of NPs at various concentrations, even up to 25 mg/mL (the original NPs suspension), suggesting that PLGA-based …”

Interaction and Localization of Synthetic Nanoparticles in Healthy and Cystic Fibrosis Airway Epithelial Cells: Effect of Ozone Exposure

“…(42) Nuclear entry of polylysine nanoparticles (73 nm hydrodynamic diameter) was also observed in chochlear cells. (42,43) Further confirmatory methods may be required to study this phenomenon.…”