PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma
PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma
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聚乙二醇化聚酰胺胺树枝状聚合物与肿瘤归巢肽缀合作为神经胶质瘤的潜在靶向递送系统
DOI：
10.1016/j.colsurfb.2016.08.002
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发表时间：
2016-11-01
影响因子：
5.8
通讯作者：
Xu, Qunwei
中科院分区：
文献类型：
--
作者：
Jiang, Yan;Lv, Lingyan;Xu, Qunwei
多形性胶质母细胞瘤（GBM）是最常见、侵袭性最强的原发性中枢神经系统（CNS）肿瘤，生存期短。化疗失败的原因是化疗药物通过血脑肿瘤屏障（BBTB）的运输低，渗透到肿瘤组织的能力差。为了克服这两个障碍，迫切需要具有主动靶向能力的小纳米颗粒用于GBM药物递送。在本研究中，我们提出了聚乙二醇化聚氨基酰胺（PAMAM）树状分子纳米粒子结合胶质瘤自导肽（Pep-1）作为潜在的胶质瘤靶向递送系统（Pep-PEG-PAMAM），其中聚乙二醇化PAMAM树状分子纳米粒子由于其体积小且完全穿透肿瘤，被用作载体，Pep-1通过白细胞介素13受体α 2 （IL-13R α 2）介导的内吞作用来克服BBTB。初步评价了Pep-PEG-PAMAM作为胶质瘤纳米载体的可用性和安全性。体外实验结果表明，U87 MG细胞内吞Pep-PEG-PAMAM的量显著增加。U87MG荷瘤小鼠体内荧光成像证实，靶向组胶质瘤部位荧光强度比非靶向组高2.02倍（**p < 0.01），胶质瘤分布实验进一步显示，Pep-PEG-PAMAM在肿瘤部位的蓄积和渗透明显增强。总之，Pep-1修饰的PAMAM是一种很有前景的靶向递送脑胶质瘤的纳米载体。(C) 2016 Elsevier B.V.版权所有
Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor alpha 2 (IL-13R alpha 2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p < 0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. (C) 2016 Elsevier B.V. All rights reserved.