https://scholars.lib.ntu.edu.tw/handle/123456789/400668
標題: | Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA-b-PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells | 作者: | Trong-Ming Don Kun-Ying Lu Li-Jie Lin CHUN-HUA HSU Jui-Yu Wu Fwu-Long Mi |
關鍵字: | enzymatic digestion; N-isopropylacrylamide; nanogels; pH-responsive; protamine; thermoresponsive | 公開日期: | 十一月-2017 | 來源出版物: | Molecular Pharmaceutics | 摘要: | 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. ? 2017 American Chemical Society. |
URI: | https://doi.org/10.1021/acs.molpharmaceut.7b00737 http://scholars.lib.ntu.edu.tw/handle/123456789/400668 |
DOI: | 10.1021/acs.molpharmaceut.7b00737 | SDG/關鍵字: | copolymer; doxorubicin; enzyme; nanocarrier; nanogel; photosensitizing agent; protein; rose bengal; unclassified drug; acrylic acid resin; antineoplastic agent; doxorubicin; drug carrier; nanoparticle; photosensitizing agent; poly-N-isopropylacrylamide; protamine; Article; breast cancer; cell proliferation; cell viability; cellular distribution; conformational transition; controlled drug release; cytotoxicity; drug delivery system; drug efficacy; drug synthesis; hydrolysis; in vitro study; MCF-7 cell line; NCI-ADR-RES cell line; pH; phase transition; photocytotoxicity; photodynamic therapy; polymerization; priority journal; protein conformation; surface charge; temperature; tumor microenvironment; breast tumor; cell membrane permeability; chemistry; drug effect; drug resistance; gel; human; multidrug resistance; pathology; pH; photochemotherapy; procedures; temperature; Acrylic Resins; Antineoplastic Agents; Breast Neoplasms; Cell Membrane Permeability; Doxorubicin; Drug Carriers; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gels; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Protamines; Temperature; Tumor Microenvironment |
顯示於: | 農業化學系 |
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