摘要
蛋白酶参与与肿瘤发展和进展相关的各种过程。由于它们在细胞外基质和基底层降解中的整体作用,它们在癌细胞迁移,侵入,血管生成和转移中起重要作用。它们还涉及癌细胞信号转导,上皮 - 间质转化,抗肿瘤免疫应答,细胞去分化和癌症干细胞重塑。他们参与pro-tumorigenic过程使他们有趣的抗癌治疗的目标。最有希望的是基质金属蛋白酶,半胱氨酸组织蛋白酶,尿激酶型纤溶酶原激活剂系统和蛋白酶体;这些构成了本次审查的重点。已经开发了几种抑制剂来降低处于不同发育阶段的活性,其中一些已经在临床使用中。然而,蛋白酶抑制剂的全身性递送可导致正常组织中蛋白水解活性的不希望的降低,导致不良作用和有限的治疗功效。这个警告可以通过将蛋白酶抑制剂特异性导向癌细胞的纳米颗粒递送系统来规避。在本文中,我们回顾了将蛋白酶抑制剂递送至癌细胞的纳米粒子递送系统的当前状态。
关键词: 纳米颗粒,药物递送,蛋白酶,蛋白酶抑制剂,癌细胞,水解。
Current Medicinal Chemistry
Title:Nanoparticle Based Delivery of Protease Inhibitors to Cancer Cells
Volume: 24 Issue: 42
关键词: 纳米颗粒,药物递送,蛋白酶,蛋白酶抑制剂,癌细胞,水解。
摘要: Proteases are involved in a variety of processes associated with tumor development and progression. Because of their integral role in extracellular matrix and basal lamina degradation they play important roles in cancer cell migration, invasion, angiogenesis and metastasis. They are also involved in cancer cell signaling, the epithelial-mesenchymal transition, the antitumor immune response, cell de-differentiation and cancer stem cell remodeling. Their involvement in pro-tumorigenic processes makes them interesting targets for anticancer therapy. The most promising are matrix metalloproteases, cysteine cathepsins, the urokinase-type plasminogen activator system and proteasome; these constitute the focus of this review. Several inhibitors have been developed for reducing their activities that are in different phases of development, with some already in clinical use. However, systemic delivery of protease inhibitors can result in undesired reduction of proteolytic activity in normal tissues, leading to adverse effects and limited therapeutic efficacy. This caveat can be circumvented by nanoparticle delivery systems that direct protease inhibitors specifically to cancer cells. In this article we review the current state of nanoparticle delivery systems for delivering protease inhibitors to cancer cells.
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Nanoparticle Based Delivery of Protease Inhibitors to Cancer Cells, Current Medicinal Chemistry 2017; 24 (42) . https://dx.doi.org/10.2174/0929867323666160922162811
DOI https://dx.doi.org/10.2174/0929867323666160922162811 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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