Multiple hydrogen-bonded supramolecular polymers tend to form stable spherical micelles with oppositely charged anticancer drugs in biological environments, which improves cellular drug uptake and more effectively induces apoptosis in cancer cells.
pH-Responsive hydrogen-bonded supramolecular micelles, composed of a water-soluble poly(ethylene glycol) polymer with two terminal sextuple hydrogen bonding groups, can spontaneously organize in aqueous media to give well-defined, uniformly sized spherical micelles. The supramolecular micelles exhibit a number of unique physical characteristics, such as interesting amphiphilic behavior, desirable micellar size and nanospherical morphology, excellent biocompatibility, tailorable drug-loading capacities, and high structural stability in media containing serum or red blood cells. In addition, the drug release kinetics of drug-loaded micelles can be easily manipulated to achieve the desired release profile by regulating the environmental pH, thus these micelles are highly attractive candidates as an intelligent drug carrier system for cancer therapy. Cytotoxicity assays showed that the drug-loaded micelles induced pH-dependent intracellular drug release and exerted strong antiproliferative and cytotoxic activities toward cancer cells. Importantly, cellular uptake and flow cytometric analyses confirmed that a mildly acidic intracellular environment significantly increased cellular internalization of the drug-loaded micelles and subsequent drug release in the cytoplasm and nucleus of cancer cells, resulting in more effective induction of apoptotic cell death. Thus, this system may provide an efficient route toward achieving the fundamental properties and practical realization of pHsensitive drug-delivery systems for chemotherapy.
The conventional mucking system of tunnel construction in China has a series of deficiencies and stubborn problems. Tunnel mucking technologies matched with different tunnel construction methods have been analyzed systematically and the continuous belt mucking methodology which is appropriated with drilling-blasting method was presented. The continuous belt mucking technology includes mucking scheme design and mucking equipment configuration. Compared with the conventional mucking methods, the comprehensive benefit can be fully demonstrated by the new continuous belt mucking system. On the other hand, the predominance on environmental protection of the continuous belt mucking technoloty matches up with the conservation policy. The technology would be widely applied in long tunnels and tunnels embedded in frozen ground and located in bitter cold plateau. The economic benifis and contribution to society of continuous belt mucking technology would be remarkable.
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