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      pH-responsive micelles based on (PCL) 2(PDEA- b-PPEGMA) 2 miktoarm polymer: controlled synthesis, characterization, and application as anticancer drug carrier


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          Amphiphilic A 2(BC) 2 miktoarm star polymers [poly(ϵ-caprolactone)] 2-[poly(2-(diethylamino)ethyl methacrylate)- b- poly(poly(ethylene glycol) methyl ether methacrylate)] 2 [(PCL) 2(PDEA- b-PPEGMA) 2] were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending on the architecture of the polymers. The self-assembled empty and doxorubicin (DOX)-loaded micelles were spherical in morphologies, and the average sizes were about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH 6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the growth of cancer cells HepG2 with IC 50 of 2.0 μg/mL. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL) 2(PDEA- b-PPEGMA) 2 micelles could be a prospective candidate as anticancer drug carrier for hydrophobic drugs with sustained release behavior.

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          Future perspectives and recent advances in stimuli-responsive materials

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            Diminishing catalyst concentration in atom transfer radical polymerization with reducing agents.

            The concept of initiators for continuous activator regeneration (ICAR) in atom transfer radical polymerization (ATRP) is introduced, whereby a constant source of organic free radicals works to regenerate the Cu(I) activator, which is otherwise consumed in termination reactions when used at very low concentrations. With this technique, controlled synthesis of polystyrene and poly(methyl methacrylate) (Mw/Mn < 1.2) can be implemented with catalyst concentrations between 10 and 50 ppm, where its removal or recycling would be unwarranted for many applications. Additionally, various organic reducing agents (derivatives of hydrazine and phenol) are used to continuously regenerate the Cu(I) activator in activators regenerated by electron transfer (ARGET) ATRP. Controlled polymer synthesis of acrylates (Mw/Mn < 1.2) is realized with catalyst concentrations as low as 50 ppm. The rational selection of suitable Cu complexing ligands {tris[2-(dimethylamino)ethyl]amine (Me6TREN) and tris[(2-pyridyl)methyl]amine (TPMA)} is discussed in regards to specific side reactions in each technique (i.e., complex dissociation, acid evolution, and reducing agent complexation). Additionally, mechanistic studies and kinetic modeling are used to optimize each system. The performance of the selected catalysts/reducing agents in homo and block (co)polymerizations is evaluated.
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              Recent progress in tumor pH targeting nanotechnology.

              pH-sensitive polymeric micelles and nanogels have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms by endosomal or lysosomal acidity plus endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. This review highlights recent progress of the pH-sensitive nanotechnology developed in Bae research group.

                Author and article information

                Nanoscale Res Lett
                Nanoscale Res Lett
                Nanoscale Research Letters
                18 May 2014
                : 9
                : 1
                : 243
                [1 ]School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China
                [2 ]School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510640, People's Republic of China
                Copyright © 2014 Lin et al.; licensee Springer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                : 26 February 2014
                : 4 May 2014
                Nano Express

                ph-responsive,polymer,micelles,drug delivery,in vitro
                ph-responsive, polymer, micelles, drug delivery, in vitro


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