Cyclodextrin-based polyrotaxanes: Cellular uptake enhancement effect of different functionality types

Four polyisoprene-based polyrotaxanes (PRX) were synthesized via rotaxa-polymerization and subsequent modification using randomly methylated β-cyclodextrin (RAMEB), hydroxypropyl β-cyclodextrin (HP-βCD), thiolated (HP-βCD-SH), and mercaptosuccinic HP-βCD (HP-βCD-MSA). The polyrotaxanes with threadin...

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Bibliographic Details
Main Authors: David Gintsburg, Pia Kreuzer, Khush Bakhat Afzal, Ilaria Polidori, Martyna Truszkowska, Anna Seybold, Andreas Bernkop-Schnürch, Gergely Kali
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893925003226
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Summary:Four polyisoprene-based polyrotaxanes (PRX) were synthesized via rotaxa-polymerization and subsequent modification using randomly methylated β-cyclodextrin (RAMEB), hydroxypropyl β-cyclodextrin (HP-βCD), thiolated (HP-βCD-SH), and mercaptosuccinic HP-βCD (HP-βCD-MSA). The polyrotaxanes with threading efficacies of 36–42%, molar masses of 45–50 kDa, and particle sizes ranging from 32 to 105 nm exhibit high cell viability and lipase-mediated biodegradation. The cell internalization of these polymeric supramolecular systems was investigated through flow cytometry and confocal microscopy on Caco-2 and HEK293 cells. The results indicate an increase in cellular uptake for all PRXs compared to the free β-CD derivative, with the highest enhancement observed for the RAMEB-, followed by HP-βCD- and HP-βCD-SH-based systems, while the lowest was noted with the anionic HP-βCD-MSA. This work demonstrates direct and indirect effects of functional groups of polyrotaxanes on cellular internalization, providing crucial findings for the development of a new polyrotaxane-based treatment for lysosomal storage disorders through intracellular delivery of these cyclic oligosaccharides.
ISSN:2666-8939