Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA‑b‑PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells
學年 106
學期 1
出版（發表）日期 2017-10-23
作品名稱 Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA‑b‑PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells
作品名稱（其他語言）
著者 Trong-Ming Don; Kun-Ying Lu; Li-Jie Lin; Chun-Hua Hsu; Jui-Yu Wu; Fwu-Long Mi
單位
出版者
著錄名稱、卷期、頁數 Molecular Pharmaceutics 14(12), p.4648−4660
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.
關鍵字 N-isopropylacrylamide;enzymatic digestion;nanogels;pH-responsive;protamine;thermoresponsive
語言 en_US
ISSN 1543-8384
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Fwu-Long Mi
審稿制度 是
國別 USA
公開徵稿
出版型式 ,電子版
相關連結

機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/113021 )