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Combination Glioma Therapy Mediated by a Dual‐Targeted Delivery System Constructed Using OMCN–PEG–Pep22/DOX
Small ( IF 13.0 ) Pub Date : 2018-09-14 , DOI: 10.1002/smll.201801905 Wenbo Qian 1 , Min Qian 2 , Yi Wang 3 , Jianfei Huang 4 , Jian Chen 1 , Lanchun Ni 1 , Qingfeng Huang 1 , Qianqian Liu 1 , Peipei Gong 1 , Shiqiang Hou 1 , Hui Zhu 5 , Zhongzheng Jia 6 , Dandan Shen 6 , Changlai Zhu 7 , Rui Jiang 1 , Junlong Sun 1 , Junzhong Yao 1 , Zhongyu Tang 1 , Xiang Ji 1 , Jinlong Shi 1 , Rongqin Huang 2 , Wei Shi 1
Small ( IF 13.0 ) Pub Date : 2018-09-14 , DOI: 10.1002/smll.201801905 Wenbo Qian 1 , Min Qian 2 , Yi Wang 3 , Jianfei Huang 4 , Jian Chen 1 , Lanchun Ni 1 , Qingfeng Huang 1 , Qianqian Liu 1 , Peipei Gong 1 , Shiqiang Hou 1 , Hui Zhu 5 , Zhongzheng Jia 6 , Dandan Shen 6 , Changlai Zhu 7 , Rui Jiang 1 , Junlong Sun 1 , Junzhong Yao 1 , Zhongyu Tang 1 , Xiang Ji 1 , Jinlong Shi 1 , Rongqin Huang 2 , Wei Shi 1
Affiliation
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Accumulating studies have investigated the efficacy of receptor‐mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low‐density lipoprotein receptor (LDLR) is designed to generate a novel drug‐loaded system, designated as OMCN–PEG–Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood–brain barrier and exerts therapeutic efficacy through both near‐infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma‐killing temperature in a glioma‐bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug‐loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR‐overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near‐infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug‐loaded system as a promising drug delivery vehicle for clinical application in glioma therapy.
中文翻译：
使用OMCN–PEG–Pep22 / DOX构建的双靶点递送系统介导的联合胶质瘤治疗
越来越多的研究调查了受体介导的疏水性药物在神经胶质瘤化疗中的疗效。在这里，包含聚乙二醇（PEG）和与Pep22多肽连接的氧化纳米晶介孔碳颗粒（OMCN）靶向低密度脂蛋白受体（LDLR）的运载工具被设计为生成一个新型载药系统，称为OMCN– PEG–Pep22 / DOX（OPPD）。该系统可有效靶向神经胶质瘤细胞和血脑屏障，并通过强力霉素（DOX）的近红外（NIR）光热和化学治疗作用发挥治疗作用。病理组织微阵列显示人脑胶质瘤组织中LDLR过表达与患者生存率相关。NIR辐射治疗和磁共振成像结果表明，OPPD在具有颅骨去除模型的荷胶质瘤大鼠中达到了有效的胶质瘤杀伤温度，并且相对于未经Pep22肽修饰和控制的载药系统，胶质瘤的大小明显减小分别。因此，OPPD不仅有效地靶向过表达LDLR的神经胶质瘤，而且还通过将DOX转运到神经胶质瘤中并通过近红外辐射产生热效应杀死肿瘤细胞而发挥双重治疗作用。这些共同的发现支持了新型OPPD载药系统作为一种有前景的药物输送工具，可用于神经胶质瘤治疗的临床应用。
更新日期：2018-09-14
中文翻译：
使用OMCN–PEG–Pep22 / DOX构建的双靶点递送系统介导的联合胶质瘤治疗
越来越多的研究调查了受体介导的疏水性药物在神经胶质瘤化疗中的疗效。在这里，包含聚乙二醇（PEG）和与Pep22多肽连接的氧化纳米晶介孔碳颗粒（OMCN）靶向低密度脂蛋白受体（LDLR）的运载工具被设计为生成一个新型载药系统，称为OMCN– PEG–Pep22 / DOX（OPPD）。该系统可有效靶向神经胶质瘤细胞和血脑屏障，并通过强力霉素（DOX）的近红外（NIR）光热和化学治疗作用发挥治疗作用。病理组织微阵列显示人脑胶质瘤组织中LDLR过表达与患者生存率相关。NIR辐射治疗和磁共振成像结果表明，OPPD在具有颅骨去除模型的荷胶质瘤大鼠中达到了有效的胶质瘤杀伤温度，并且相对于未经Pep22肽修饰和控制的载药系统，胶质瘤的大小明显减小分别。因此，OPPD不仅有效地靶向过表达LDLR的神经胶质瘤，而且还通过将DOX转运到神经胶质瘤中并通过近红外辐射产生热效应杀死肿瘤细胞而发挥双重治疗作用。这些共同的发现支持了新型OPPD载药系统作为一种有前景的药物输送工具，可用于神经胶质瘤治疗的临床应用。
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