Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme
Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme
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DOI：
10.1158/1535-7163.mct-06-0480
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发表时间：
2006-12-01
影响因子：
5.7
通讯作者：
Connor, James R.
中科院分区：
文献类型：
--
作者：
Madhankumar, A. B.;Slagle-Webb, Becky;Connor, James R.
与恶性脑肿瘤的治疗相关的困难是有据可查的。例如，高级别星形细胞瘤的局部浸润阻止了所有恶性细胞的完全切除。因此，关键是开发用于化学治疗剂的递送系统，其消融个体癌细胞而不对周围脑组织造成扩散性损伤。在这里，我们描述了空间稳定的人白细胞介素-13（IL-13）缀合脂质体，其有效地结合到过表达IL-13受体α 2蛋白的脑癌细胞。结合脂质体结合多形性胶质母细胞瘤组织标本，但不正常皮质。将脂质体与人IL-13缀合允许特异性结合神经胶质瘤细胞并通过内吞作用摄取脂质体。与递送游离药物相比，通过IL-13缀合的脂质体将阿霉素递送至胶质瘤细胞导致增强的细胞毒性和增加的药物在胶质瘤细胞中的积累和保留。使用皮下注射法在体内测试携带阿霉素的IL-13缀合的脂质体的治疗潜力和靶向功效。神经胶质瘤小鼠模型。接受IL-13偶联脂质体（携带阿霉素）腹腔注射7周的动物，平均肿瘤体积为37 mm 3，而注射非靶向脂质体的动物平均肿瘤体积为192 mm 3。这些结果强烈表明，IL-13缀合的脂质体携带细胞毒性剂是一种可行的方法，用于创建用于脑肿瘤治疗的纳米囊泡药物递送系统。
The difficulties associated with treatment of malignant brain tumors are well documented. For example, local infiltration of high-grade astrocytomas prevents the complete resection of all malignant cells. It is, therefore, critical to develop delivery systems for chemotherapeutic agents that ablate individual cancer cells without causing diffuse damage to surrounding brain tissue. Here, we describe sterically stable human interieukin-13 (IL-13)-conjugated liposomes, which efficiently bind to the brain cancer cells that overexpress the IL-13 receptor alpha 2 protein. The conjugated liposomes bind to glioblastoma multiforme tissue specimens but not to normal cortex. Conjugating the liposomes with human IL-13 allows for specific binding to glioma cells and uptake of the liposomes via endocytosis. Delivering doxorubicin to glioma cells by IL-13-conjugated liposomes results in enhanced cytotoxicity and increased accumulation and retention of drug in the glioma cells compared with delivery of free drug. The therapeutic potential and targeting efficacy of the IL-13-conjugated liposomes carrying doxorubicin was tested in vivo using a s.c. glioma tumor mouse model. Animals receiving i.p. injections of IL-13 -conjugated liposomes carrying doxorubicin for 7 weeks had a mean tumor volume of 37 mm(3) compared with a mean volume of 192 mm(3) in animals injected with nontargeted liposomes. These results strongly suggest that IL-13-conjugated liposomes carrying cytotoxic agents are a feasible approach for creating a nanovesicle drug delivery system for brain tumor therapy.