Synthesis of self-assemble pH-responsive cyclodextrin block copolymer for sustained anticancer drug delivery
Tóm tắt
Well-defined pH-responsive poly(ε-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers (PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and “click” chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), and gel permeation chromatography (GPC). Then, the polymers could selfassemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin (DOX) release, and these results revealed 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 88% (W/W). CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.
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