No abstract

Inspired by glucose-sensitive ion channels, herein we describe a biomimetic glucose-enantiomer-driven ion gate via the introduction of the chiral pillar[6]arene-based host–guest systems into the artificial nanochannels. The chiral nanochannels show a high chiral-driven ionic gate for glucose enantiomers and can be switched “off” by d-glucose and be switched “on” by l-glucose. Remarkably, the chiral nanochannel also exhibited a good reversibility toward glucose enantiomers. Further research indicates that the switching behaviors differed due to the differences in binding strength between chiral pillar[6]arene and glucose enantiomers, which can lead to the different surface charge within nanochannel. Given these promising results, the studies of chiral-driven ion gates may not only give interesting insight for the research of biological and pathological processes caused by glucose-sensitive ion channels, but also help to understand the origin of the high stereoselectivity in life systems.

The light-controlled gating of ion transport across membranes is central to nature (e.g., in protein channels). Herein, inspired by channelrhodopsins, we introduce a facile non-covalent approach towards light-responsive biomimetic channelrhodopsin nanochannels using host–guest interactions between a negative pillararene host and a positive azobenzene guest. By switching between threading and dethreading states with alternating visible and UV light irradiation, the functional channels can be flexible to regulate the inner surface charge of the channels, which in turn was exploited to achieve different forms of ion transport, for instance, cation-selective transport and anion-selective transport. Additionally, the pillararene-azobenzene-based nanochannel system could be used to construct a light-activated valve for molecular transport. Given these promising results, we suggest that this system could not only provide a better understanding of some biological processes, but also be applied for drug delivery and various biotechnological applications.

Herein, based on biomimetic strategies, a tunable mercury(ii) ion-gate modulated by mercaptoacetic acid-pillar[5]arene (MAP5) is reported.

The MDR can be roughly divided into intrinsic resistance and acquired resistance. [2] The intrinsic drug resistance is related to the altered expression or mutation of BCL-2-related apoptotic proteins and is independent of drug efflux pumps. Notably, the members of BCL-2 protein family (e.g., BAX (a proapoptotic p53 transcriptional target) and BCL-2 (an antiapoptotic factor)) can primarily regulate the mitochondrial apoptotic pathway and the relative ratio of BAX to BCL-2 determines a threshold for the induction of apoptosis. [3] While, the acquired resistance, usually arising during the chemotherapy of relapsing leukemia and ovarian and breast cancers, [3b] results from the overexpression of cell membrane-bound adenosine triphosphate (ATP)-binding cassette (ABC) transporters that can recognize and catalyze the efflux of diverse hydrophobic anticancer drugs from cells, lowering the intracellular accumulation of anticancer drugs and reducing their therapeutic effect. [1a] One of the transporters, P-glycoprotein (P-gp), can pump out many drugs such as doxorubicin, paclitaxel, vinblastine, and so on. The other transporter is breast cancer resistance protein (BCRP), an ABC half-transporter, which is derived from a doxorubicin-resistant MCF-7 breast cancer cell line and resists doxorubicin and camptothecins. [4] Both P-gp and BCRP contribute to form a unique defense against chemotherapeutics and reduce the intracellular drug accumulation.To reverse or evade the mechanism of MDR and improve the efficacy of chemotherapy, many efforts have been made for the last decades. Diverse nanocarrier-based drug delivery strategies with combinations of multiple drugs, which can bypass the drug efflux pumps through endocytic pathways and lysosomal delivery, have been successfully developed to evade MDR in cancer therapy. [5] These nanocarriers include several main modalities. One is to directly suppress the function of P-gp using surfactants (e.g., pluronic P123 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)) which deplete ATP production, or to directly inactivate P-gp with a relevant inhibitor (e.g., apatinib (AP) and disulfiram). [6] Another one is based on RNA interference technology. This strategy is mainly by loading small interfering RNA (siRNA), which can specifically knock down the expression of drug resistance-related genes, to restore the chemosensitivity of cancer cells. [7] The third one is to design a Multiple drug resistance (MDR) of cancer cells is a major cause of chemotherapy failure. It is currently a great challenge to develop a direct and effective strategy for continuously inhibiting the P-glycoprotein (P-gp) drug pump of MDR tumor cells, thus enhancing the intracellular concentration of the therapeutic agent for effectively killing MDR tumor cells. Here, a new implantable hierarchical-structured ultrafine fiber device is developed via a microfluidic-electrospinning technology for localized codelivery of doxorubicin (DOX) and apatinib (AP). An extremely high encapsulation efficiency of ≈99% fo...