Polymer-coated pH-responsive high-density lipoproteins
Polymer-coated pH-responsive high-density lipoproteins
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DOI：
10.1016/j.jconrel.2016.03.005
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发表时间：
2016-04-28
影响因子：
10.8
通讯作者：
Murakami, Tatsuya
中科院分区：
文献类型：
--
作者：
Kim, Hyungjin;Okamoto, Haruki;Murakami, Tatsuya
通过纳米颗粒的细胞内药物递送通常受到其内体包埋，随后在溶酶体隔室和/或胞吐中降解的阻碍。在这里，我们表明，内化和内涵体逃逸的货物在阳离子化的天然纳米载体，高密度脂蛋白（HDL），可以控制在pH值依赖性的方式通过稳定的络合与膜溶解阴离子嵌段聚合物。首次通过与YGRKKRRQRRR肽的基因融合和1，2-二油酰氧基-3-（三甲基铵）丙烷的掺入制备了HDL的基因和化学阳离子化形式（catHDL）。加入聚（乙二醇）-嵌段-聚（甲基丙烯酸丙酯-共-甲基丙烯酸）（PA）后，catHDL在中性pH下抑制内化，随后在弱酸性pH下恢复。直径50 nm），甚至在血清存在下。在用catHDL/PA处理人癌细胞1小时后，观察到catHDL组分的内体逃逸的显著增强。与catHDL相比，多柔比星和姜黄素这两种荧光抗癌药物在catHDL/PA中也被转运到内体外，其细胞毒性在细胞内增强。这些数据表明，catHDL/PA可能具有改善治疗剂在弱酸性条件下（如在肿瘤组织中）的细胞递送和内体逃逸的潜在益处。(C)2016爱思唯尔B. V.保留所有权利。
Intracellular drug delivery by nanoparticles is often hampered by their endosomal entrapment followed by their degradation in the lysosomal compartment and/or exocytosis. Here, we show that internalization and endosomal escape of cargoes in a cationized natural nanocarrier, high-density lipoprotein (HDL), can be controlled in a pH-dependent manner through stable complexation with a membranolytic anionic block polymer. A genetically and chemically cationized form of HDL (catHDL) is prepared for the first time by both genetic fusion with YGRKKRRQRRR peptide and incorporation of 1,2-dioleoyloxy-3-(trimethylammonium) propane. Upon addition of poly(ethylene glycol)-block-poly(propyl methacrylate-co-methacrylic acid) (PA), catHDL yields inhibition of internalization at neutral pH and its subsequent recovery at mildly acidic pH. catHDL forms a stable discoidal-shape complex with PA (catHDL/PA) (ca. 50 nm in diameter), even in the presence of serum. Significant enhancement of endosomal escape of a catHDL component is observed after a 1-h treatment of human cancer cells with catHDL/PA. Doxorubicin and curcumin, fluorescent anti-cancer drugs, encapsulated into catHDL/PA are also translocated outside of endosomes, compared with that into catHDL, and their cytotoxicities are enhanced inside the cells. These data suggest that catHDL/PA may have a potential benefit to improve the cellular delivery and endosomal escape of therapeutics under mildly acidic conditions such as in tumor tissues. (C) 2016 Elsevier B.V. All rights reserved.