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Biocompatible Poly(2-hydroxyethyl methacrylate)-b-poly(L-histidine) Hybrid Materials for pH-Sensitive Intracellular Anticancer Drug Delivery

Authors

  • Renjith P. Johnson,

    1. The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea
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  • Young-Il Jeong,

    1. National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan 626-870, Korea
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  • Eunji Choi,

    1. The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea
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  • Chung-Wook Chung,

    1. National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan 626-870, Korea
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  • Dae Hwan Kang,

    1. National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan 626-870, Korea
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  • Sae-Ock Oh,

    1. Department of Anatomy, Pusan National University, Yangsan 626-870, Korea
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  • Hongsuk Suh,

    1. Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Pusan 609-735, Korea
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  • Il Kim

    Corresponding author
    1. The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea
    • The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea.
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Abstract

A series of synthetic polymer bioconjugate hybrid materials consisting of poly(2-hydroxyethyl methacrylate) (p(HEMA)) and poly(l-histidine) (p(His)) are synthesized by combining atom transfer radical polymerization of HEMA with ring opening polymerization of benzyl-N-carboxy-L-histidine anhydride. The resulting biocompatible and membranolytic p(HEMA)25-b-p(His)n (n = 15, 25, 35, and 45) polymers are investigated for their use as pH-sensitive drug-carrier for tumor targeting. Doxorubicin (Dox) is encapsulated in nanosized micelles fabricated by a self-assembly process and delivered under different pH conditions. Micelle size is characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) observations. Dox release is investigated according to pH, demonstrating the release is sensitive to pH. Antitumor activity of the released Dox is assessed using the HCT 116 human colon carcinoma cell line. Dox released from the p(HEMA)-b-p(His) micelles remains biologically active and has the dose-dependent capability to kill cancer cells at acidic pH. The p(HEMA)-b-p(His) hybrid materials are capable of self-assembling into nanomicelles and effectively encapsulating the chemotherapeutic agent Dox, which allows them to serve as suitable carriers of drug molecules for tumor targeting.

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