期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 6, 期 7, 页码 4096-4105出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c00644
关键词
self-complementary sextuple hydrogen bonding interaction; controlled drug delivery; supramolecular micelles; pH-responsiveness; self-assembly
资金
- Ministry of Science and Technology, Taiwan [MOST 107-2221-E-011041-MY3]
- Taipei Medical University-National Taiwan University of Science and Technology Joint Research Program [TMU-NTUST-109-03]
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 pH-sensitive drug-delivery systems for chemotherapy.
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