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Drug and plasmid DNA co-delivery nanocarriers based on abctype polypeptide hybrid miktoarm star copolymers

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Abstract

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(ɛ-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(ɛ-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.

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Authors and 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  (刘世勇)

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  1. Tao Liu
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  2. Yan-feng Zhang
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  3. Shi-yong Liu  (刘世勇)
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Correspondence to Shi-yong Liu  (刘世勇).

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Invited paper dedicated to Professor Fosong Wang on the occasion of his 80th birthday

Electronic Supplementary Material Supplementary material is available in the online version of this article at http//dx.doi.org/10.1007/s10118-013-1281-0.

The work was financially supported by the National Natural Science Foundation of China (Nos. 21274137, 91027026 and 51033005), Fundamental Research Funds for the Central Universities, and Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP, 20123402130010).

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Liu, T., Zhang, Yf. & Liu, Sy. Drug and plasmid DNA co-delivery nanocarriers based on abctype polypeptide hybrid miktoarm star copolymers. Chin J Polym Sci 31, 924–937 (2013). https://doi.org/10.1007/s10118-013-1281-0

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  • DOI: https://doi.org/10.1007/s10118-013-1281-0

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