We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly（ethylene oxide）, poly（L-lysine）, and poly（e-caprolactone） arms, PEO（-b-PLL）-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO（-b-PZLL）-b-PCL, were synthesized at first via the combination of consecutive ＂click＂ reactions and ring-opening polymerizations （ROP）, where PZLL is poly（e-benzyloxycarbonyl-L-lysine）. Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO（-b-PLL）-b-PCL. In aqueous media at pH 7.4, PEO（-b-PLL）-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA （pDNA） at N/P ratios higher than ca. 2. Thus, PEO（-b-PLL）-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO（-b- PLL）-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.
We report on the fabrication of fluorescent and multicolor probes for Zn^2＋ ions and temperature from a mixture of three types of fluorophore-labeled responsive block copolymers in aqueous media. Quinoline-based Zn^2＋-recognizing fluorescent mono- mer ZQMA, red-emitting rhodamine B-based monomer RhBEA, and blue-emitting coumarin derivative Coum-OH, were syn- thesized first. A ZQMA-labeled well-defined double hydrophilic block copolymer （DHBC）, PEG-b-P（MEO2MA-co-ZQMA）, was synthesized via reversible addition-fragmentation chain-transfer （RAFT） polymerization of 2-（2-methoxyethoxy）ethyl methacrylate （MEOzMA） and ZQMA by utilizing a PEG-based macroRAFT agent. Following similar procedures, PEG-b-P（St-co-RhBEA） amphiphilic diblock copolymer and PEG-b-P（MEOzMA-co-Coum） DHBC were also synthesized, where P（St-co-RhBEA） was a RhBEA-labeled polystyrene （PS） block. At room temperature in aqueous solution, almost non- fluorescent PEG-b-P（MEOzMA-co-ZQMA） can effectively bind Zn2＋ ions, leading to prominent green fluorescence enhance- ment due to the coordination of ZQMA with Zn^2＋ ions. However, by mixing red-emitting PEG-b-P（St-co-RhBEA） and blue-emitting PEG-b-P（MEO2MA-co-Coum） with PEG-b-P（MEO2MA-co-ZQMA） at an appropriate ratio, three color transitions could be observed. In the absence of Zn^2＋ ions, a mixed pink fluorescent originating from Coum and RhBEA was ob- served; upon the addition of a certain amount of Zn^2＋ ions, the green fluorescence enhanced dramatically, leading to a white fluorescence readout. By further increasing the amount of Zn2＋ ions, the green fluorescence further enhanced and overwhelmed the blue and red emissions, leading to a green-dominant mixed-fluorescence emission. In addition, upon increasing the temperature, the fluorescence of Coum decreased considerably due to the fluorescence-resonance energy transfer （FRET） between Coum and ZQMA moieties. In this way, a ratiometric fluorescent thermometer can be constructed.
HU XiangLongLI YangLIU TaoZHANG GuoYingLIU ShiYong
