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基于纳米粒子的脑递药系统与抗血管生成在脑胶质瘤治疗中的应用。

Nanoparticle-based cerebral drug-delivery systems and antiangiogenic approach in gliomas treatment.

机构信息

Neurosurgical Clinic, Department of Neurosciences, Psychiatry and Anesthesiology, A.O.U. Policlinico G. Martino, via Consolare Valeria, 1, 98125 Messina, Italy.

出版信息

Recent Pat Nanotechnol. 2011 Nov;5(3):239-44. doi: 10.2174/1872210511105030239.

Abstract

The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.

摘要

当前针对神经胶质瘤的抗癌多模态治疗策略的疗效受到缺乏针对恶性细胞的特异性治疗方法的限制,并且脑胶质瘤患者的预后仍然非常不利。当胶质瘤与细胞外基质结合时,通过上调血管生成和侵袭等关键途径,似乎能够为肿瘤细胞的侵袭创造有利的环境。脑内药物输送的主要问题是血脑屏障的存在,这限制了许多化疗药物和其他治疗分子的输送。这种情况常常导致治疗失败。纳米颗粒系统可以作为将特定化合物递送至穿过血脑屏障的脑肿瘤的理想装置。杂交的特异性使反义方法成为一种有前途的策略,可以选择性地调节参与肿瘤发生的基因的表达。在这篇综述中,我们将重点讨论血管生成进入神经胶质瘤的机制、它们在肿瘤进展中的重要性,以及用新的基于纳米颗粒的治疗策略来阻断这些机制的可能性。我们还将报告在脑胶质瘤中采用基于纳米颗粒的抗血管生成治疗方法的临床前和/或临床研究结果,同时还考虑了一些涉及抗血管生成策略的专利。

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