Zhao Yijun, Ouyang Xumei, Peng Yongjun, Peng Shaojun
Zhuhai Institute of Translational Medicine, Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, China.
The Department of Medical Imaging, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, China.
Pharmaceutics. 2021 Nov 12;13(11):1917. doi: 10.3390/pharmaceutics13111917.
Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development.
气体疗法作为一种新兴且有前景的癌症治疗方法，已受到医学界的广泛关注。在所有气体分子中，一氧化氮（NO）因其有趣的性质和独特的抗肿瘤机制，成为近年来的研究热点，是首个应用于生物医学领域的气体分子。尽管NO在癌症治疗方面取得了巨大进展，但其在体内的非特异性分布以及高浓度时对正常组织的副作用，阻碍了其临床应用。因此，开发简便的基于NO的纳米药物，以实现肿瘤组织中NO的按需释放，同时避免NO在正常组织中的泄漏，从而在提高治疗效果的同时减少副作用，具有重要意义。近年来，众多研究报道了基于外源性刺激（光、超声、X射线）或肿瘤内源性信号（谷胱甘肽、弱酸、葡萄糖）触发的基于NO的纳米药物的设计与开发。在本综述中，我们总结了基于NO的纳米药物在各种刺激下的设计原则、释放行为及其在协同癌症治疗中的应用。我们还讨论了基于NO的纳米药物在体内增强癌症治疗的抗肿瘤机制。此外，为了推动该领域的进一步发展，我们讨论了该领域目前存在的挑战和未来展望。
