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Updated: Jul 26, 2025

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape
Özlem Kaplan1, Martyna Truszkowska2, Gergely Kali2
1Department of Genetics and Bioengineering, Rafet Kayış Faculty of Engineering, Alanya Alaaddin Keykubat University, 07400 Antalya, Turkey; Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, 34134 Istanbul, Turkey.
Abstract:
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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