Synthesis and Characterization of pH-Responsive PEG-Poly(β-Amino Ester) Block Copolymer Micelles as Drug Carriers to Eliminate Cancer Stem Cells
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2020
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Abstract
PEG-poly(β-amino ester) (PEG-PBAE), which is an effective pH-responsive copolymer, was mainly synthesized by Michael step polymerization. Thioridazine (Thz), which was reported to selectively eliminate cancer stem cells (CSCs), was loaded into PEG-PBAE micelles (PPM) prepared by self-assembly at low concentrations. The critical micelle concentrations (CMC) of PPM in water were 2.49 μg/mL. The pH-responsive PBAE segment was soluble due to protonated tertiary amine groups when the pH decreased below pH 6.8, but it was insoluble at pH 7.4. The Thz-loaded PEG-PBAE micelle (Thz/PPM) exhibited a spherical shape, and the drug loading was 15.5%. In vitro release of Thz/PPM showed that this pH-sensitivity triggered the rapid release of encapsulated Thz in a weakly acidic environment. The in vitro cytotoxicity and cellular uptake of various formulations at pH 7.4 and 5.5 were evaluated on the mammospheres (MS), which were sorted by MCF-7 human breast cancer cell lines and identified to be a CD44+/CD24− phenotype. The results of the cytotoxicity assay showed that blank micelles were nontoxic and Thz/PPM exhibited a similar anti-CSC effect on MS compared to Thz solution. Stronger fluorescence signal of Coumarin-6 (C6) was observed in MS treated by C6-loaded PPM (C6/PPM) at pH 5.5. The tumor inhibition rate and tumor weight of the free DOX and Thz/PPM groups were significantly different from those of the other groups, which free DOX and Thz/PPM effectively suppressed breast tumor growth in vivo. The above experimental results showed that Thz/PPM is an ideal and effective pH-responsive drug delivery carrier to a targeted therapy of CSCs.
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wang2020pharmaceuticssynthesis
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| Authors | Weinan Li,Jialin Sun,Xiaoyu Zhang,Li Jia,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Da-Wei Chen,Yanhong Wang;Weinan Li;Jialin Sun;Xiaoyu Zhang;Li Jia;Mingxi Qiao;Xiuli Zhao;Haiyang Hu;Da-Wei Chen;Yanhong Wang; |
| Journal | Pharmaceutics |
| Year | 2020 |
| DOI |
10.3390/pharmaceutics12020111
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| URL | |
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