1. Investigating the Effect of Esterification on Retinal Pigment Epithelial Uptake Using Rhodamine B Derivatives
- Author
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Chandima Bulumulla, Timothy D. Nguyen, Mihaela C. Stefan, Timothy Catchpole, Alison Takacs, Alexa Gilfoyle, Ruvanthi N. Kularatne, Karl G. Csaky, and Abigail Christie
- Subjects
0301 basic medicine ,Biomedical Engineering ,Retinal Pigment Epithelium ,Mitochondrion ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,fluorescent probes ,Live cell imaging ,Extracellular ,medicine ,Rhodamine B ,age-related macular degeneration ,Retinal pigment epithelium ,Esterification ,Rhodamines ,Chemistry ,Biological Transport ,Retinal ,mitochondria ,Ophthalmology ,030104 developmental biology ,medicine.anatomical_structure ,Lipophilicity ,030221 ophthalmology & optometry ,Biophysics ,Retinal Pigments ,cellular penetration ,Intracellular - Abstract
Purpose This study investigated the effects of esterification and increased lipophilicity on cellular penetration, accumulation and retention in ARPE-19-nic cells using ester functionalized rhodamine B dyes. Methods Rhodamine B was esterified to generate four dyes with increasing lipophilicity. Cellular uptake, retention and mitochondrial localization were investigated in vitro using ARPE-19-nic cells using direct intracellular and extracellular and mitochondrial fluorescence quantitation, confocal and high-resolution live cell imaging and co-localization with Mito-GFP. Results Cellular penetrance, mitochondrial accumulation, and retention of the esterified dyes were increased in ARPE-19-nic cells compared with the nonesterified parent dye by direct fluorescence quantitation. Imaging demonstrated intracellular accumulation was confined to mitochondria as confirmed by colocalization with Mito-GFP. Conclusions Esterification is an effective way to increase lipophilicity of a dye to improve cellular penetration of chemical entities. These observations may be key to improving retinal drug delivery for retinal pigment epithelium-based diseases. Translational relevance Understanding the intracellular distribution of drugs into retinal pigment epithelium cells is a critical component for identifying potential therapies for retinal pigment epithelium-based diseases. more...
- Published
- 2020
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