Environmental stimuli-responsive nucleobase-functionalized supramolecular polymers, a combination of oligomeric polypropylene glycol segments as a thermosensitive element and hydrogen-bonded uracil as a photosensitive moiety, were successfully developed and undergo spontaneous self-assembly to form uniform nanosized micelles via self-complementary double hydrogen bonding interactions between the uracil moieties in an aqueous environment. These micelles exhibit unique properties such as dual thermo-and photoresponsiveness, controllable lower critical concentration solution temperature (LCST), photoreactivity, and morphological transformation, making them highly attractive for various applications. More importantly, phase transitions and morphological studies confirmed the LCST behavior, size, and shape of the micelles can be easily tuned by adjusting the concentration and duration of ultraviolet irradiation of samples in aqueous solution, indicating introduction of uracil molecules into a water-soluble polymer matrix may represent a promising approach toward development of multiple stimuliresponsive polymeric micelles whose self-assembly behavior can be manipulated. In view of the ease of fabrication, high biocompatibility, multifunctionality, and tailorable micellar properties, this newly developed supramolecular micelle may be a promising candidate nanocarrier for controlled drug delivery and bioimaging systems.
Self-assembled pH-responsive polymeric micelles, a combination of hydrophilic poly(ethylene glycol) segments and hydrogen bonding interactions within a biocompatible polyurethane substrate, can spontaneously self-assemble into highly controlled, nanosized micelles in aqueous solution. These newly developed micelles exhibit excellent pH-responsive behavior and biocompatibility, highly controlled drug (doxorubicin; DOX) release behavior, and high drug encapsulation stability in different aqueous environments, making the micelles highly attractive potential candidates for safer, more effective drug delivery in applications such as cancer chemotherapy. In addition, in vitro cell studies revealed the drug-loaded micelles possessed excellent drug entrapment stability and low cytotoxicity toward macrophages under normal physiological conditions (pH 7.4, 37 °C). When the pH of the culture media was reduced to 6.0 to mimic the acidic tumor microenvironment, the drug-loaded micelles triggered rapid release of DOX within the cells, which induced potent antiproliferative and cytotoxic effects in vitro. Importantly, fluorescent imaging and flow cytometric analyses confirmed the DOX-loaded micelles were efficiently delivered into the cytoplasm of the cells via endocytosis and then subsequently gradually translocated into the nucleus. Therefore, these multifunctional micelles could serve as delivery vehicles for precise, effective, controlled drug release to prevent accumulation and activation of tumor-promoting tumor-associated macrophages in cancer tissues. Thus, this unique system may offer a potential route toward the practical realization of next-generation pH-responsive therapeutic delivery systems.
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