Supramolecular nanogels cross-linked by host–guest interaction between dextran grafted benzimidazole (Dex-g-BM) and thiol-β-cyclodextrin were designed. Their special supramolecular pH-sensitivity under acidic conditions (pH < 6, within the range of malignant cellular endosomes) and reduction sensitivity in response to biologically relevant stimuli will be of great advantage to the future of cancer chemotherapeutics.

Intracellular pH-sensitive supramolecular block amphiphiles based on the host–guest interaction between benzimidazole (BM) modified poly(ε-caprolactone) (BM-PCL) and cyclodextrin (β-CD) terminated dextran (Dex-β-CD) were designed. The supramolecular block amphiphiles could further self-assemble into supramolecular micelles and exhibit pH-sensitive behaviour in acidic aqueous solution when the pH value was below 6. Doxorubicin (DOX), a model anticancer drug, was effectively loaded into the supramolecular micelles via hydrophobic interactions. The DOX release from all DOX-loaded micelles was accelerated in acid conditions mimicking the endosomal/lysosomal compartments. The enhanced intracellular DOX release was observed in HepG2 cells. DOX-loaded intracellular pH-sensitive supramolecular micelles showed higher cellular proliferation inhibition towards HepG2 cells than pH-insensitive micelles. These features suggested that the supramolecular micelles could efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a powerful mean for delivering and releasing cargoes at the tumor sites.

A series of pH/reduction dual responsive poly(ethylene glycol)/polyurethane triblock copolymers containing tertiary amines and disulfide bonds are reported. The polyurethane block copolymers self-assembled into stable micelles in aqueous medium at pH 7.4, which responded rapidly to both a narrow pH change within the physiologically relevant pH range and a reduction environment mimicking the intracellular space. The in vitro drug release from doxorubicin (DOX)-loaded polyurethane micelles was significantly accelerated by reducing the pH or by addition of an intracellular reducing agent, glutathione (GSH). Confocal laser scanning microscopy (CLSM) and flow cytometry measurements revealed that the intracellular drug release from the DOX-loaded nanoparticles was increased in the HeLa cells with enhanced intracellular GSH level. In addition, even though the polyurethane block copolymers exhibited good cytocompatibility, the DOX-loaded polyurethane micelles displayed efficient growth inhibition of HeLa and HepG2 cells, which showed a dependence on the intracellular GSH concentration. Owing to their unique responsiveness to dual biological stimuli, the biocompatible and bioreducible polyurethane block copolymers have the potential to serve as a versatile platform for intracellular drug delivery.

The solid state and melt nanoscale structures of a series of poly(ethylene glycol)-block-poly(γ-alkyl-l-glutamate)s (PEG-b-PALG) copolymers bearing different alkyl side groups, i.e., n-butyl, n-hexyl, n-octyl, and n-dodecyl, have been investigated in the present work. An interesting effect of alkyl side groups on the secondary conformation of polypeptide block, crystallization of PEG segments and morphology of the copolymers was observed. With increasing the length of alkyl side groups or raising the temperature, the predominant secondary structure gradually changed from α-helix to β-sheet conformation. Differential scanning calorimetry, wide-angle X-ray diffraction analysis and polarized optical microscopy indicated that the crystallization and morphology of PEG segments were markedly restricted by the polypeptide block. Therefore, the alkyl side groups not only exhibited significant influence on the conformation of polypeptide block, but also affected the crystallization of PEG segments. The secondary structure, crystallization and spherulite morphology of these synthetic biomaterials, which were significantly influenced by alkyl side groups, may play an important role in their physicochemical properties, such as self-assembly, as well as in some biomedical applications.

Supramolecular nanogels cross-linked by host–guest interaction between dextran grafted benzimidazole (Dex-g-BM) and thiol-β-cyclodextrin were designed. Their special supramolecular pH-sensitivity under acidic conditions (pH < 6, within the range of malignant cellular endosomes) and reduction sensitivity in response to biologically relevant stimuli will be of great advantage to the future of cancer chemotherapeutics.