| Chemotherapy is one of the main means of cancer treatment,but the large toxic side effects on normal cells often lead to the failure of cancer treatment.With the development of nanotechnology,various smart nano drug delivery systems with targeting ability,biodegradability and stimuli responsiveness provided great possibilities for solving the problem.Pillar[n]arenes as a new generation of macrocyclic molecules,have many excellent properties in host-guest chemistry compared with other macrocyclic molecules.They had been widely used to construct smart drug delivery systems.The modification of different groups could endow the systems targeting and stimulating response ability.The diselenide bond could be cleaved under different conditions,and the conditions required for stimuli response were milder than that for disulfide bonds,so it could be used to the construction of responsive materials.In this study,we reported a new redox-responsive supramolecular nano vesicles based on the host-guest interaction between the diselenide pillar[5]arene and mannose derivative.The cleavage of the diselenide bond could be caused by the high GSH concentration in tumor microenvironment,and the mannose derivative could endow the system cancer cell targeting ability by the specially recognition between mannose and mannose receptor which was overexpressed on the surfaces of MCF-7 cells and Hep G2 cells.More importantly,the mannose derivative could improve the solubility and stability of the system.The nano vesicles demonstrated to be effective for the encapsulation,targeted delivery and controlled release of drugs.Thereby the DOX-loaded vesicles could not only effectively killing the cancer cells,but also reduce the toxicity to normal cells.The main research contents of this paper include:(1)Preparation and characterization of DOX-loaded vesicles: The morphology,diameter and drug loading/release profile of the DOX-loaded vesicles were studied by using scanning electron microscope,transmission electron microscope,dynamic light scattering,Ultraviolet–visible spectroscopy and surface tension meter.The results showed that the critical aggregation concentration was 10.4 μg/m L and the average sizes of nano vesicles before and after drug loading were 270 nm and 319 nm.So the drug was successfully loaded into the nano vesicles and the drug loading content was 21.3%.Upon 2.5 m M GSH into the solution,the release rate reached 62% after 72 h.(2)Cell uptake and targeting studies: The DOX-loaded vesicles were incubated with Hep G2 cells and MCF-7 cells for 2,4,12 h,respectively,and the intracellular DOX fluorescence intensity was observed by confocal laser scanning microscope.The results showed that the fluorescence intensity was increased by incubated time.With the same incubated time,the fluorescence intensity of the group which was preincubated with mannose was significantly decreased.The results were also confirmed by flow cytometry.It indicated that the DOX-loaded vesicles could be taken up by Hep G2 cells and MCF-7 cells.Otherwise,it also indicated that the targeting ability of the drug delivery system.(3)Cytotoxicity studies: The cytotoxicity of system was studied by using MTT assay.The results showed that the system had no obvious cytotoxicity.The DOX-loaded vesicles had higher cytotoxicity to cancer cells than normal cells.Then the drug delivery system could reduce the toxic side effects of free DOX.In summary,this study constructed a smart supramolecular nano drug delivery system based on diselenide pillar[5]arene,and the fabrication and application of the system were studied.The experimental results showed that the system could be used for targeted delivery and stimulated response release of drugs,and could significantly reduce the toxicity and side effects of drugs.The supramolecular nano vesicles were expected to be used as a smart delivery system for anticancer drugs,and had a good application prospect. |
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