Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut.
Antioxid Redox Signal. 2019 Feb 10;30(5):747-761. doi: 10.1089/ars.2017.7370. Epub 2017 Nov 21.
The overabundance of reactive oxygen species (ROS) and antioxidants in cancer cells represents a challenge for therapeutic intervention, while also providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes. Recent Advances: Nanotechnology has advanced tremendously in recent decades and now offers many potential opportunities to leverage altered redox status to improve conventional therapies. Highly tunable nanoparticle delivery systems have shown great promise for improving the following: (i) chemotherapy via selective redox-sensitive drug release in tumor cells and limited systemic toxicity; (ii) photodynamic therapy via enhancing photoactivation and/or ROS production; and (iii) radiation therapy via enhancing ROS production. Great progress has also been made regarding novel nanoparticle-mediated therapies to enhance tumor cell death via ROS generation and angiogenic inhibition.
Current anticancer therapies are limited by systemic side effects and resistance. The inherent heterogeneity and hypoxic status of solid tumors impose significant barriers for even the most rationally designed nanoparticle systems. In addition, few comprehensive biodistribution and toxicity evaluations exist, and clinical efficacy remains to be established. The practicality of many nanoparticle systems is compromised by variable in vivo responses and scale-up difficulties due to complicated chemistry and prohibitive manufacturing costs.
As nanoparticle design continues to advance, improved therapeutic efficacy will likely follow. Actively targeted systems may improve distribution specificity but more positive clinical demonstrations are needed. Further investigation into systemic and intracellular distribution as well as toxicity will improve understanding of how these nanoparticle systems can be applied to improve existing therapies.
癌细胞中活性氧（ROS）和抗氧化剂的过剩代表了治疗干预的挑战，同时也为开发改善临床治疗效果的新策略提供了机会。
纳米技术在过去几十年中取得了巨大进展，现在为利用改变的氧化还原状态来改善传统疗法提供了许多潜在机会。高度可调的纳米颗粒输送系统在以下方面显示出巨大的潜力：（i）通过在肿瘤细胞中选择性释放氧化还原敏感药物和有限的全身毒性来进行化疗；（ii）通过增强光激活和/或 ROS 产生来进行光动力疗法；（iii）通过增强 ROS 产生来进行放射治疗。在通过 ROS 生成和血管生成抑制来增强肿瘤细胞死亡的新型纳米颗粒介导的治疗方面也取得了很大进展。
目前的抗癌疗法受到全身副作用和耐药性的限制。实体瘤固有的异质性和缺氧状态即使对最合理设计的纳米颗粒系统也构成了重大障碍。此外，几乎没有全面的生物分布和毒性评估，临床疗效仍有待确定。由于复杂的化学性质和过高的制造成本，许多纳米颗粒系统的实用性受到体内反应和扩大规模困难的影响。
随着纳米颗粒设计的不断进步，治疗效果可能会得到改善。主动靶向系统可以提高分布特异性，但需要更多积极的临床证明。进一步研究系统和细胞内分布以及毒性将有助于了解如何将这些纳米颗粒系统应用于改善现有疗法。
