Department of Pharmacology, School of Pharmacy, Nantong University, 226000, Nantong, Jiangsu, PR China.
Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Science, Health Science Center, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, 710061, Shaanxi, PR China.
Eur J Med Chem. 2020 Jun 1;195:112274. doi: 10.1016/j.ejmech.2020.112274. Epub 2020 Mar 30.
Hypoxia, a common characteristic in solid tumors, is found in phenotypically aggressive cancers that display resistance to typical cancer interventions. Due to its important role in tumor progression, tumor hypoxia has been considered as a primary target for cancer diagnosis and treatment. An advantage of hypoxia-activated nanomedicines is that they are inactive in normoxic cells. In hypoxic tumor tissues and cells, these nanomedicines undergo reduction by activated enzymes (usually through 1 or 2 electron oxidoreductases) to produce cytotoxic substances. In this review, we will focus on approaches to design nanomedicines that take advantage of tumor hypoxia. These approaches include: i) inhibitors of hypoxia-associated signaling pathways; ii) prodrugs activated by hypoxia; iii) nanocarriers responsive to hypoxia, and iv) bacteria mediated hypoxia targeting therapy. These strategies have guided and will continue to guide nanoparticle design in the near future. These strategies have the potential to overcome tumor heterogeneity to improve the efficiency of radiotherapy, chemotherapy and diagnosis.
缺氧是实体瘤的一个常见特征，存在于表现出对典型癌症干预措施的抗性的表型侵袭性癌症中。由于其在肿瘤进展中的重要作用，肿瘤缺氧已被认为是癌症诊断和治疗的主要靶点。缺氧激活型纳米药物的一个优势是在正常氧细胞中它们是无活性的。在缺氧的肿瘤组织和细胞中，这些纳米药物通过被激活的酶（通常通过 1 或 2 个电子氧化还原酶）还原，以产生细胞毒性物质。在这篇综述中，我们将重点介绍利用肿瘤缺氧的设计纳米药物的方法。这些方法包括：i）缺氧相关信号通路的抑制剂；ii）缺氧激活的前药；iii）对缺氧有反应的纳米载体，和 iv）细菌介导的缺氧靶向治疗。这些策略指导并将继续指导未来纳米颗粒的设计。这些策略有可能克服肿瘤异质性，提高放疗、化疗和诊断的效率。
