Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma
Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma
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DOI：
10.1073/pnas.1114518108
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发表时间：
2011-10-18
影响因子：
11.1
通讯作者：
Ruoslahti, Erkki
中科院分区：
文献类型：
--
作者：
Agemy, Lilach;Friedmann-Morvinski, Dinorah;Ruoslahti, Erkki
抗血管生成治疗可以使胶质母细胞瘤（GBM）的肿瘤暂时消退，但没有延长患者的生存期。我们构建了一个靶向肿瘤血管系统的纳米系统，该系统包含三个元素：（i）肿瘤归巢肽，其特异性地将其有效载荷递送至肿瘤内皮细胞和肿瘤细胞的线粒体，（ii）该归巢肽与作用于线粒体的促凋亡肽的缀合，以及（iii）在氧化铁纳米颗粒上的多价呈递，其增强促凋亡活性。纳米颗粒的氧化铁成分使小鼠GBM肿瘤成像成为可能。用纳米颗粒对携带GBM的小鼠进行全身治疗，根除了一种GBM小鼠模型中的大多数肿瘤，并显著延迟了另一种模型中的肿瘤发展。将纳米颗粒与肿瘤穿透肽共注射进一步增强了治疗效果。所使用的两种模型都被证明对其他疗法具有完全抗性，这表明我们的纳米系统具有临床潜力。
Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and (iii) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.