{"id":13800,"date":"2019-05-15T21:16:26","date_gmt":"2019-05-15T13:16:26","guid":{"rendered":"https:\/\/www.bihec.com\/olisclarity\/?p=13800"},"modified":"2019-05-18T00:12:43","modified_gmt":"2019-05-17T16:12:43","slug":"%e7%94%a8%e4%ba%8e%e8%8d%af%e7%89%a9%e8%be%93%e9%80%81%e5%88%b0%e8%82%bf%e7%98%a4%e7%bb%86%e8%83%9eph%e5%8f%af%e6%bf%80%e6%b4%bb%e7%bb%86%e8%83%9e%e7%a9%bf%e9%80%8f%e8%82%bd%e7%9a%84%e8%ae%be%e8%ae%a1","status":"publish","type":"post","link":"https:\/\/www.bihec.com\/olisclarity\/%e7%94%a8%e4%ba%8e%e8%8d%af%e7%89%a9%e8%be%93%e9%80%81%e5%88%b0%e8%82%bf%e7%98%a4%e7%bb%86%e8%83%9eph%e5%8f%af%e6%bf%80%e6%b4%bb%e7%bb%86%e8%83%9e%e7%a9%bf%e9%80%8f%e8%82%bd%e7%9a%84%e8%ae%be%e8%ae%a1\/","title":{"rendered":"\u7528\u4e8e\u836f\u7269\u8f93\u9001\u5230\u80bf\u7624\u7ec6\u80depH\u53ef\u6fc0\u6d3b\u7ec6\u80de\u7a7f\u900f\u80bd\u7684\u8bbe\u8ba1"},"content":{"rendered":"<p>Design of a new pH\u2010activatable cell\u2010penetrating peptide for drug delivery into tumor cells<br \/>\n\u7528\u4e8e\u836f\u7269\u8f93\u9001\u5230\u80bf\u7624\u7ec6\u80depH\u53ef\u6fc0\u6d3b\u7ec6\u80de\u7a7f\u900f\u80bd\u7684\u8bbe\u8ba1<\/p>\n<p>Abstract<br \/>\n\u6458\u8981<\/p>\n<p>Cell penetrating peptides (CPPs) were considered as potential drug delivery vectors due to their remarkable membrane translocation capacity. However, lack of specificity and extreme systemic toxicity hamper their successful application for drug delivery. Here, we designed a new pH\u2010activatable CPP, LHHLLHHLHHLLHH\u2010NH2 (LH), by substitution of all lysines and two leucines of LKKLLKLLKKLLKL\u2010NH2 (LK) with histidines. As expected, histidine\u2010rich LH could be activated and penetrate into cells at pH 6.0, whereas its membrane transduction activity could be shielded at pH 7.4. In contrast, LK showed no obviously different cellular uptake at both pH conditions. Importantly, LH was significantly less cytotoxicity compared with LK at both pH values, suggesting a better safety for further application. In addition, after conjugation of camptothecin (CPT) with LH, this conjugate displayed remarkably pH\u2010dependent antitumor activity than free CPT and LK\u2010CPT. This study provides a new tumor pH\u2010responsive CPP with low toxicity for selective anticancer drug delivery.<\/p>\n<p>\u7ec6\u80de\u7a7f\u900f\u80bd\uff08CPPs\uff09\u7531\u4e8e\u5176\u663e\u8457\u7684\u819c\u6613\u4f4d\u80fd\u529b\u800c\u88ab\u8ba4\u4e3a\u662f\u6f5c\u5728\u7684\u836f\u7269\u8f93\u9001\u8f7d\u4f53\u3002\u7136\u800c\uff0c\u7f3a\u4e4f\u7279\u5f02\u6027\u548c\u6781\u7aef\u7684\u5168\u8eab\u6bd2\u6027\u59a8\u788d\u4e86\u5b83\u4eec\u836f\u7269\u8f93\u9001\u7684\u6210\u529f\u7387\u3002\u73b0\u5728\uff0c\u6211\u4eec\u8bbe\u8ba1\u4e86\u4e00\u79cd\u65b0\u7684pH\u53ef\u6fc0\u6d3b\u7ec6\u80de\u7a7f\u900f\u80bd\uff0cLHHLLHHLHHLLHH\u2010NH2 (LH)\uff0c\u6765\u53d6\u4ee3\u6240\u6709\u8d56\u6c28\u9178\u548cLKKLLKLLKKLLKL\u2010NH2 (LK) +\u7ec4\u6c28\u9178\u4e24\u79cd\u4eae\u6c28\u9178\u3002\u6b63\u5982\u9884\u671f\u7684\u90a3\u6837\uff0c\u5bcc\u542b\u7ec4\u6c28\u9178\u7684LH\u53ef\u4ee5\u5728pH 6.0\u4e0b\u88ab\u6fc0\u6d3b\u5e76\u6e17\u900f\u5230\u7ec6\u80de\u4e2d\uff0c\u800c\u5176\u819c\u8f6c\u5bfc\u6d3b\u6027\u53ef\u4ee5\u5728pH 7.4\u4e0b\u88ab\u5c4f\u853d\u3002\u76f8\u53cd\uff0cLK\u5728\u4e24\u79cdpH\u6761\u4ef6\u4e0b\u5747\u672a\u663e\u793a\u51fa\u660e\u663e\u4e0d\u540c\u7684\u7ec6\u80de\u6444\u53d6\u3002\u91cd\u8981\u7684\u662f\uff0c\u4e0eLK\u76f8\u6bd4\uff0cLH\u5728\u4e24\u79cdpH\u503c\u4e0b\u7684\u7ec6\u80de\u6bd2\u6027\u663e\u7740\u964d\u4f4e\uff0c\u8868\u660e\u8fdb\u4e00\u6b65\u5e94\u7528\u5177\u6709\u66f4\u597d\u7684\u5b89\u5168\u6027\u3002\u6b64\u5916\uff0c\u5728\u559c\u6811\u78b1\uff08CPT\uff09\u4e0eLH\u7f00\u5408\u540e\uff0c\u8be5\u7f00\u5408\u7269\u663e\u793a\u51fa\u6bd4\u6e38\u79bbCPT\u548cLK-CPT\u663e\u8457\u7684pH\u4f9d\u8d56\u6297\u80bf\u7624\u6d3b\u6027\u3002\u8be5\u7814\u7a76\u63d0\u4f9b\u4e86\u4e00\u79cd\u65b0\u7684\u4f4e\u6bd2\u6027\u80bf\u7624pH\u54cd\u5e94CPP\uff0c\u6765\u8f93\u9001\u9009\u5b9a\u7684\u6297\u764c\u836f\u7269\u3002<\/p>\n<p>\u9996\u6b21\u53d1\u8868: 2019-5-6: <a href=\"https:\/\/doi.org\/10.1111\/cbdd.13537\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/doi.org\/10.1111\/cbdd.13537<\/a><\/p>\n<p><a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/dsm-17\/\" title=\"View all posts in DSM 17\" target=\"_blank\">DSM 17<\/a> <a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/cd%e5%9c%86%e4%ba%8c%e8%89%b2%e5%85%89%e8%b0%b1%e4%bb%aa\/\" title=\"View all posts in CD\u5706\u4e8c\u8272\u5149\u8c31\u4eea\" target=\"_blank\">CD\u5706\u4e8c\u8272\u5149\u8c31\u4eea<\/a> \u5e94\u7528<\/p>\n<br><div class=\"tagcloud\"><a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/cd%e5%85%89%e8%b0%b1%e4%bb%aa\/\" class=\"tag-cloud-link tag-link-0 tag-link-position-1\" style=\"font-size: 22pt;\" aria-label=\"CD\u5149\u8c31\u4eea (84\u4e2a\u9879\u76ee)\">CD\u5149\u8c31\u4eea<\/a>\n<a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/%e5%9c%86%e4%ba%8c%e8%89%b2\/\" class=\"tag-cloud-link tag-link-1 tag-link-position-2\" style=\"font-size: 8pt;\" aria-label=\"\u5706\u4e8c\u8272 (34\u4e2a\u9879\u76ee)\">\u5706\u4e8c\u8272<\/a>\n<a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/%e5%9c%86%e4%ba%8c%e8%89%b2cd\/\" class=\"tag-cloud-link tag-link-2 tag-link-position-3\" style=\"font-size: 9.4358974358974pt;\" aria-label=\"\u5706\u4e8c\u8272CD (37\u4e2a\u9879\u76ee)\">\u5706\u4e8c\u8272CD<\/a>\n<a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/%e5%9c%86%e4%ba%8c%e8%89%b2%e5%85%89%e8%b0%b1%e4%bb%aa\/\" class=\"tag-cloud-link tag-link-3 tag-link-position-4\" style=\"font-size: 20.564102564103pt;\" aria-label=\"\u5706\u4e8c\u8272\u5149\u8c31\u4eea (76\u4e2a\u9879\u76ee)\">\u5706\u4e8c\u8272\u5149\u8c31\u4eea<\/a>\n<a href=\"https:\/\/www.bihec.com\/olisclarity\/tag\/%e5%9c%86%e4%ba%8c%e8%89%b2%e8%b0%b1\/\" class=\"tag-cloud-link tag-link-4 tag-link-position-5\" style=\"font-size: 9.0769230769231pt;\" aria-label=\"\u5706\u4e8c\u8272\u8c31 (36\u4e2a\u9879\u76ee)\">\u5706\u4e8c\u8272\u8c31<\/a><\/div>","protected":false},"excerpt":{"rendered":"<p>Design of a new pH\u2010activatable cell\u2010penetrating peptide for drug delivery into tumor cells <\/p>\n","protected":false},"author":7,"featured_media":60,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_vp_format_video_url":"","_vp_image_focal_point":[]},"categories":[1],"tags":[15,11,18,4,12],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v17.5 - 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