Jiangsu Clinical Medicine Centre of Tissue Engineering and Nerve Injury Repair, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
Small. 2018 Oct;14(42):e1801905. doi: 10.1002/smll.201801905. Epub 2018 Sep 14.
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.
已有多项研究探讨了受体介导的疏水性药物在神经胶质瘤化疗中的递送效果。在此，设计了一种由聚乙二醇（PEG）和连接到靶向低密度脂蛋白受体（LDLR）的 Pep22 多肽的氧化纳米晶介孔碳颗粒（OMCN）组成的递药载体，以生成一种新型载药系统，命名为 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，并通过负载的多西环素（DOX）的近红外（NIR）光热和化疗作用发挥治疗效果。组织病理微阵列显示人神经胶质瘤组织中 LDLR 过表达与患者生存相关。NIR 照射治疗和磁共振成像结果表明，在颅骨切除模型的荷瘤大鼠中，OPPD 达到有效杀伤神经胶质瘤的温度，并与未进行 Pep22 肽修饰的载药系统和对照组相比，显著减小神经胶质瘤的大小。因此，OPPD 不仅能有效靶向 LDLR 过表达的神经胶质瘤，还能通过将 DOX 转运至神经胶质瘤并利用近红外照射产生热效应杀死肿瘤细胞，发挥双重治疗作用。这些研究结果表明，新型 OPPD 载药系统作为一种有前途的神经胶质瘤治疗临床应用的药物递送载体具有应用潜力。
