DRUG AND PLASMID DNA CO-DELIVERY NANOCARRIERS BASED ON ABCTYPE POLYPEPTIDE HYBRID MIKTOARM STAR COPOLYMERS
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DRUG AND PLASMID DNA CO-DELIVERY NANOCARRIERS BASED ON ABCTYPE POLYPEPTIDE HYBRID MIKTOARM STAR COPOLYMERS
Chinese Journal of Polymer ScienceVol. 31, Issue 6, Pages: 924-937(2013)
Affiliations:
1.CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China
Tao Liu, Yan-feng Zhang, Shi-yong Liu. DRUG AND PLASMID DNA CO-DELIVERY NANOCARRIERS BASED ON ABCTYPE POLYPEPTIDE HYBRID MIKTOARM STAR COPOLYMERS. [J]. Chinese Journal of Polymer Science 31(6):924-937(2013)
DOI:
Tao Liu, Yan-feng Zhang, Shi-yong Liu. DRUG AND PLASMID DNA CO-DELIVERY NANOCARRIERS BASED ON ABCTYPE POLYPEPTIDE HYBRID MIKTOARM STAR COPOLYMERS. [J]. Chinese Journal of Polymer Science 31(6):924-937(2013) DOI: 10.1007/s10118-013-1281-0.
DRUG AND PLASMID DNA CO-DELIVERY NANOCARRIERS BASED ON ABCTYPE POLYPEPTIDE HYBRID MIKTOARM STAR COPOLYMERS
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(,ε,-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(,ε,-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.
关键词
Keywords
Miktoarm star copolymersGene deliveryCo-deliveryPolypeptideSelf-assembly