| Micelles formed from synthetic amphiphilic biodegradable block copolymers have been extensively exploited to improve conventional cancer therapy in drug delivery system (DDS) in recent years, because it could increase drug stability, drug solubility, and passive target effects due to their core-shell geometry. There has been marked progress in the search for stimulus-responsive nanoparticles. It would be difficult to meet so many stimulus-responsive requirements for just a single micelle system in DDS. Thereby, the mixed micelle system (MMS) may be a good choice to accommodate the stimulus-responsive behaviors of micelles. Furthermore, many anticancer drug loaded micelle systems have no obvious selectivity to cell types, which would also have high toxicity against normal cells. Consequently, tumor selective strategies via cellular receptors in targeted gene and drug delivery is so necessary.This paper also research in this respect, the major results are as follows:Firstly, A series of amphiphilic poly(ether-ester) block polymers composed of Pluronic F127 andε-caprolactone were synthesized. The resultant terpolymers were characterized by Fourier transform infrared spectroscopy (FT-IR),1H-nuclear magnetic resonance spectroscopy (1H-NMR), gel permeation chromatography (GPC), X-ray diffraction (XRD), differential scanning calorimeter (DSC) and polarization optical microscope (POM). They can self-assemble into micelles in water by solvent evaporation method. The morphologies of micelles with different lengths of CL were characterized by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The dynamic light scattering measurements (DLS) indicated that the diameter of F200 micelle was typically in the range of 100-150 nm.And then, the mixed micelles composed of F200 and bovine serum albumin (BSA) or polylactic acid (PLA) were then fabricated for application as promising drug carriers. The thermosensitive behaviors of F200 pure micelle and the mixed micelles were characterized by DLS and UV-Vis. The release of DOX.HCl-loaded pure F200, BSA/F200 and PLA/F200 mixed micelles were investigated at pH7.4 and pH5.0. As observed from cell cytotoxicity, the block polymers are of excellent biocompatibility and the DOX.HCl-loaded pure and mixed micelles are effective to inhibit the growth of HepG2 tumor cells.Finally, for cancer therapy, folate (FA) andβ-cyclodextrin (β-CD)-decorated micelles based on the biodegradable pluronic F127-b-poly(s-caprolactone) copolymer were fabricated. The resultant polymers were characterized by FT-IR,1H-NMR. These micelles were measured by the dynamic light scattering measurements (DLS) and atomic force microscopy (AFM). The in vitro release of DOX.HCl from the biodegradable polymer micelles was performed at pH7.4 and pH5.0 at the temperatures of 4,25 and 37℃, respectively. The materials cytotoxicity and the tumor cell growth inhibition assays of DOX.HCl loaded micelles were studied with human hepatoblastoma cell line (HepG2), lung epithelial cancer cell lines (A549), human nasopharyngeal epidermoid carcinoma cells (KB) and fibroblast normal cells using fluorescence microscope as well as confocal laser scanning microscope (CLSM). The cellular uptake was quantitatively analyzed to further evaluate the active-targeting behaviors of the micelles by a flow cytometry. These quantitative and qualitative results of cellular uptake of the micelles provide evidence for the different targeting efficiency of FA decoration for HepG2, KB and A549 cells and fibroblast normal cells. It may be suggested that FA andβ-CD-decorated doxorubicin-loaded micelles may be great potential as nanocarriers for targeting drug delivery. |
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