Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA‑b‑PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells

doi:10.1021/acs.molpharmaceut.7b00737

淡江大學機構典藏 > 工學院 > 化學工程與材料工程學系暨研究所 > 期刊論文 > Item 987654321/113021

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題名:	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
關鍵詞:	N-isopropylacrylamide;enzymatic digestion;nanogels;pH-responsive;protamine;thermoresponsive
日期:	2017-12-04
上傳時間:	2018-03-29 12:11:04 (UTC+8)
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.
關聯:	Molecular Pharmaceutics 14(12), p.4648−4660
DOI:	10.1021/acs.molpharmaceut.7b00737
顯示於類別:	[化學工程與材料工程學系暨研究所] 期刊論文

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