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A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD-PDA) is mucoadhesive and resistant to the digestion with ∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131 μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131 μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Star-shaped glycopolymers due to the attractive combination of the physicochemical, morphological, self-assembly properties along with biological activity have gained increased attention as innovative agents in novel cancer therapies. Unfortunately, the production of these highly desirable biomaterials remains a challenge in modern macromolecular chemistry. The main reason for that is the low polymerizability of ionic glycomonomers originated from their steric congestion and the occurrence of ionic interactions that generally negatively influence the polymerization progress and hinder controllable reaction pathway. In this work, the new ionic sugar monomer was (co)polymerized for the first time via Activator Generated by Electron Transfer Atom Transfer Radical Polymerization (AGET ATRP) using a three-arm resveratrol-based core to obtain star-like (co)polymers. The obtained products were examined in terms of their physicochemical properties and morphology. Aside from the synthesis of these new glycopolymers, also a thorough description of their thermal properties, ability to self-assembly, the formation of stable superstructures was studied in detail. It was found that examined (co)polymers did not show any heterogeneities and phase separation, while their variation of glass transition temperature (Tg) was strictly related to the change in the number of glycomonomer. Also, the stability and shapes of formed superstructures strictly depend on their composition and topology. Finally, we have shown that synthesized carbohydrate-based polymers revealed high antiproliferative activity against several cancer cell lines (i.e., breast, colon, glioma, and lung cancer). The cytotoxic activity was particularly observed for star-shaped polymers that were systematically enhanced with the growing concentration of amine moieties and molecular weight. The results presented herein suggest that synthesized star-shaped glyco(co)polymers are promising as drug or gene carriers in anticancer therapies or anti-tumor agents, depending on their cytotoxicity. [ABSTRACT FROM AUTHOR]