Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape
Carbohydrate Polymers, vol.316, 2023 (SCI-Expanded)
- Publication Type: Article / Article
- Volume: 316
- Publication Date: 2023
- Doi Number: 10.1016/j.carbpol.2023.121070
- Journal Name: Carbohydrate Polymers
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
- Keywords: Cellular uptake, Cyclodextrin, Endosomal escape, Thiol-mediated cellular uptake, Thiolated cyclodextrin
- Istanbul University Affiliated: Yes
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.