Subcellular-Scale Drug Transport via Ultrasound-Degradable Mesoporous Nanosilicon to Bypass Cancer Drug Resistance
Subcellular-Scale Drug Transport via Ultrasound-Degradable Mesoporous Nanosilicon to Bypass Cancer Drug Resistance
复制标题
通过超声可降解介孔纳米硅进行亚细胞尺度药物运输以绕过癌症耐药性
DOI：
10.1002/smll.201604228
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发表时间：
2017
期刊：
影响因子：
13.3
通讯作者：
Chen Hong-Yuan
中科院分区：
文献类型：
--
作者：
Kang Bin;Zheng Ming-Bo;Song Pei;Chen Ai-Ping;Wei Ji-Wu;Xu Jing-Juan;Shi Yi;Chen Hong-Yuan
以受控的方式将抗癌剂直接递送和释放到其亚细胞作用靶点几乎是药理学的最终目标，但它具有挑战性。近几十年来，人们做出了大量努力将药物输送到肿瘤组织，甚至专门输送到癌细胞;然而，在亚细胞规模上，癌细胞有多种狡猾的方式来阻碍药物达到其最终作用目标。在这里，我们展示了一种通过在亚细胞水平上控制药物转运和释放来绕过癌症耐药性的最后防线的策略。我们开发了一种基于超声可降解介孔纳米硅的平台，该平台允许药物递送，超声控制药物释放到细胞核中。这种策略改变了药物在细胞内的分布，并显著提高了药物在作用靶点（即细胞核）的蓄积率。体外和体内研究证明，该策略将药物剂量降低了一个数量级，延长了药物保留时间，并增强了荷瘤小鼠的治疗效果。这些结果为通过运输绕过癌症耐药性提供了新的见解，并以受控的方式将药物直接释放到其作用靶点。
Delivering and releasing anticancer agents directly to their subcellular targets of action in a controlled manner are almost the ultimate goal of pharmacology, but it is challenging. In recent decades, plenty of efforts have been made to send drugs to tumor tissue or even specifically to cancer cells; however, at the subcellular scale, cancer cells have multiple cunning ways to hinder drugs from reaching their final action targets. Here, we demonstrate a strategy to bypass the last defense of cancer drug resistance by contolling the drug transportation and release at subcellular scale. We developed a platform based on ultrasound‐degradable mesoporous nanosilicon, which allows drug delivery towards, ultrasound controlled drug release into the cell nucleus. This strategy altered the drug distribution within cells and remarkably enhanced the drug accumulation ratio at the action target, i.e. nucleus. In vitro and in vivo studies proved that this strategy reduced the drug dosage by an order of magnitude, prolonged drug retention and amplified therapeutic efficacy in tumor‐bearing mice. These results offer new insights into bypassing cancer drug resistance through transport and release drugs directly to their action targets in a controlled manner.