Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape
This study aimed to evaluate the effect of thiolated α-cyclodextrin (α-CD-SH) on the cellular uptake of its payload.
For this purpose, α-CD was thiolated using phosphorous pentasulfide. Thiolated α-CD was characterized by FT-IR and 1H NMR spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Cytotoxicity of α-CD-SH was evaluated on Caco-2, HEK 293, and MC3T3 cells. Dilauryl fluorescein (DLF) and coumarin-6 (Cou) serving as surrogates for a pharmaceutical payload were incorporated in α-CD-SH, and cellular uptake was analyzed by flow cytometry and confocal microscopy. Endosomal escape was investigated by confocal microscopy and hemolysis assay.
Results showed no cytotoxic effect within 3 h, while dose-dependent cytotoxicity was observed within 24 h. The cellular uptake of DLF and Cou was up to 20- and 11-fold enhanced by α-CD-SH compared to native α-CD, respectively. Furthermore, α-CD-SH provided an endosomal escape.
According to these results, α-CD-SH is a promising carrier to shuttle drugs into the cytoplasm of target cells.
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Phosphorus pentasulfide, tetramethylene sulfone, dimethyl sulfoxide-d6, 7-hydroxy-3H-phenoxazin-3-one-10-oxide sodium salt (Alamar Blue, Resazurin sodium salt), L-cysteine hydrochloride, coumarin-6 and dilauryl fluorescein were ordered from Sigma-Aldrich, Austria. Alpha cyclodextrin (α-CD) was purchased from Cyclolab, Hungary. 5,5′-Dithiobis(2-nitrobenzoic acid) (Ellman’s reagent) and Triton™ X-100 were obtained from Merck, Germany. NucSpot Live 650 was ordered from Biotum, America. Minimum essential eagle medium (MEM), alpha MEM and OptiMEM were obtained from ThermoFisher Scientific, Austria.
Özlem Kaplan, Martyna Truszkowska, Gergely Kali, Patrick Knoll, Mariana Blanco Massani, Doris Elfriede Braun, Andreas Bernkop-Schnürch, Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape, Carbohydrate Polymers, 2023, 121070, ISSN 0144-8617, https://doi.org/10.1016/j.carbpol.2023.121070.
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