Li Xianqiang, Wu Yue, Zhang Rui, Bai Wei, Ye Tiantian, Wang Shujun
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Front Mol Biosci. 2021 Jul 1;8:683519. doi: 10.3389/fmolb.2021.683519. eCollection 2021.
Over the past five years, oxygen-based nanocarriers (NCs) to boost anti-tumor therapy attracted tremendous attention from basic research and clinical practice. Indeed, tumor hypoxia, caused by elevated proliferative activity and dysfunctional vasculature, is directly responsible for the less effectiveness or ineffective of many conventional therapeutic modalities. Undeniably, oxygen-generating NCs and oxygen-carrying NCs can increase oxygen concentration in the hypoxic area of tumors and have also been shown to have the ability to decrease the expression of drug efflux pumps (e.g., P-gp); to increase uptake by tumor cells; to facilitate the generation of cytotoxic reactive oxide species (ROS); and to evoke systematic anti-tumor immune responses. However, there are still many challenges and limitations that need to be further improved. In this review, we first discussed the mechanisms of tumor hypoxia and how it severely restricts the therapeutic efficacy of clinical treatments. Then an up-to-date account of recent progress in the fabrications of oxygen-generating NCs and oxygen-carrying NCs are systematically introduced. The improved physicochemical and surface properties of hypoxia alleviating NCs for increasing the targeting ability to hypoxic cells are also elaborated with special attention to the latest nano-technologies. Finally, the future directions of these NCs, especially towards clinical translation, are proposed. Therefore, we expect to provide some valued enlightenments and proposals in engineering more effective oxygen-based NCs in this promising field in this comprehensive overview.
在过去五年中，用于增强抗肿瘤治疗的氧基纳米载体（NCs）引起了基础研究和临床实践的极大关注。事实上，由增殖活性升高和血管功能障碍导致的肿瘤缺氧，直接导致了许多传统治疗方式疗效不佳或无效。不可否认，产氧纳米载体和携氧纳米载体可以提高肿瘤缺氧区域的氧浓度，并且还显示出具有降低药物外排泵（如P-糖蛋白）表达的能力；增加肿瘤细胞的摄取；促进细胞毒性活性氧（ROS）的产生；以及引发全身性抗肿瘤免疫反应。然而，仍然存在许多挑战和局限性，需要进一步改进。在本综述中，我们首先讨论了肿瘤缺氧的机制以及它如何严重限制临床治疗的疗效。然后系统地介绍了产氧纳米载体和携氧纳米载体制造方面的最新进展。还特别关注最新的纳米技术，阐述了用于提高对缺氧细胞靶向能力的缺氧缓解纳米载体改善的物理化学和表面性质。最后，提出了这些纳米载体的未来方向，特别是朝着临床转化的方向。因此，我们期望通过这一全面综述，在这个有前景的领域中为设计更有效的氧基纳米载体提供一些有价值的启示和建议。
