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    Please use this identifier to cite or link to this item: http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/113021


    Title: Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA‑b‑PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells
    Authors: Trong-Ming Don;Kun-Ying Lu;Li-Jie Lin;Chun-Hua Hsu;Jui-Yu Wu;Fwu-Long Mi
    Keywords: N-isopropylacrylamide;enzymatic digestion;nanogels;pH-responsive;protamine;thermoresponsive
    Date: 2017-12-04
    Issue Date: 2018-03-29 12:11:04 (UTC+8)
    Abstract: The tumor microenvironments are often acidic and overexpress specific enzymes. In this work, we synthesized a poly(AA-b-NIPAAm) copolymer (PAA-b-PNIPAAm) using a reversible addition-fragmentation chain transfer (RAFT) polymerization method. PAA-b-PNIPAAm and a cationic protein (protamine) were self-assembled into nanogels, which effectively reduced the cytotoxicity of protamine. The protamine/PAA-b-PNIPAAm nanogels were responsive to the stimuli including temperature, pH, and enzyme due to disaggregation of PAA-b-PNIPAAm, change in random coil/α-helix conformation of protamine, and enzymatic hydrolysis of the protein. Changing the pH from 7.4 to a lowered pHe (6.5-5.0) resulted in an increase in mean particle size and smartly converted surface charge from negative to positive. The cationic nanogels easily passed through the cell membrane and enhanced intracellular localization and accumulation of doxorubicin-loaded nanogels in multidrug resistant MCF-7/ADR breast cancer cells. Cold shock treatment triggered rapid intracellular release of doxorubicin against P-glycoprotein (Pgp)-mediated drug efflux, showing significantly improved anticancer efficacy as compared with free DOX. Furthermore, the nanogels were able to carry a rose bengal photosensitizer and caused significant damage to the multidrug resistant cancer cells under irradiation. The cationic nanogels with stimuli-responsive properties show promise as drug carrier for chemotherapy and photodynamic therapy against cancers.
    Relation: Molecular Pharmaceutics 14(12), p.4648−4660
    DOI: 10.1021/acs.molpharmaceut.7b00737
    Appears in Collections:[Graduate Institute & Department of Chemical and Materials Engineering] Journal Article

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