Lei Li,Beibei Lu,Qikui Fan,Jianning Wu,Lulu Wei,Jun Hou,Xuhong Guo,Zhiyong Liu
In this work, well-defined amphiphilic polyhedral oligomeric silsesquioxane (POSS) star-shaped inorganic/organic hybrid block copolymers with poly(ε-caprolactone)-poly(2-(dimethylamino)ethyl methacrylate)-co-poly(ethylene glycol) methacrylate (POSS-PCL-P(DMAEMA-co-PEGMA))16 were synthesized with different PCL segments via thiol-ene click reaction, ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP), which were confirmed by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Subsequently, the polymers could self-assemble into micelles in aqueous solution, which were investigated by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-vis) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these triblock copolymers in water was investigated at different pH values of 5.0 and 7.4 for controlled doxorubicin release; the results indicated that the release rate of DOX could be effectively controlled by altering the pH and the release of drug loading efficiency (DLE) was up to 82% (w/w). Furthermore, CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the micelles had no associated cytotoxicity, possessed good biodegradability and biocompatibility, and identified the location of the DOX in HeLa cells. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action, and minimize the side effects of free DOX. Moreover, these flexible micelles with on-off switched drug release may offer a promising method to deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
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