Wang Xiaoxian, Li Si, Liu Xin, Wu Xian, Ye Ningbing, Yang Xiangliang, Li Zifu
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Adv Exp Med Biol. 2021;1295:77-95. doi: 10.1007/978-3-030-58174-9_4.
Nanomedicine has been a hot topic in the field of tumor therapy in the past few decades. Because of the enhanced permeability and retention effect (EPR effect), nanomedicine can passively yet selectively accumulate at tumor tissues. As a result, it can improve drug concentration in tumor tissues and reduce drug distribution in normal tissues, thereby contributing to enhanced antitumor effect and reduced adverse effects. However, the therapeutic efficacy of anticancer nanomedicine is not satisfactory in clinical settings. Therefore, how to improve the clinical therapeutic effect of nanomedicine has become an urgent problem. The grand challenges of nanomedicine lie in how to overcome various pathophysiological barriers and simultaneously kill cancer cells effectively in hypoxic tumor microenvironment (TME). To this end, the development of novel stimuli-responsive nanomedicine has become a new research hotspot. While a great deal of progress has been made in this direction and preclinical results report many different kinds of promising multifunctional smart nanomedicine, the design of these intelligent nanomedicines is often too complicated, the requirements for the preparation processes are strict, the cost is high, and the clinical translation is difficult. Thus, it is more practical to find solutions to promote the therapeutic efficacy of commercialized nanomedicines, for example, Doxil, Oncaspar, DaunoXome, Abraxane, to name a few. Increasing attention has been paid to the combination of modern advanced medical technology and nanomedicine for the treatment of various malignancies. Recently, we found that hyperbaric oxygen (HBO) therapy could enhance Doxil antitumor efficacy. Inspired by this study, we further carried out researches on the combination of HBO therapy with other nanomedicines for various cancer therapies, and revealed that HBO therapy could significantly boost antitumor efficacy of nanomedicine-mediated photodynamic therapy and photothermal therapy in different kinds of tumors, including hepatocellular carcinoma, breast cancer, and gliomas. Our results implicate that HBO therapy might be a universal strategy to boost therapeutic efficacy of nanomedicine against hypoxic solid malignancies.
在过去几十年里，纳米医学一直是肿瘤治疗领域的热门话题。由于增强的渗透与滞留效应（EPR效应），纳米医学能够被动且选择性地在肿瘤组织中蓄积。因此，它可以提高肿瘤组织中的药物浓度，并减少药物在正常组织中的分布，从而有助于增强抗肿瘤效果并降低不良反应。然而，在临床环境中，抗癌纳米医学的治疗效果并不理想。因此，如何提高纳米医学的临床治疗效果已成为一个紧迫的问题。纳米医学面临的巨大挑战在于如何克服各种病理生理障碍，并在缺氧的肿瘤微环境（TME）中同时有效地杀死癌细胞。为此，新型刺激响应性纳米医学的开发已成为一个新的研究热点。虽然在这个方向上已经取得了很大进展，并且临床前结果报告了许多不同种类的有前景的多功能智能纳米医学，但这些智能纳米医学的设计往往过于复杂，对制备过程的要求严格，成本高昂，并且临床转化困难。因此，找到提高商业化纳米医学（例如多柔比星脂质体、门冬酰胺酶、阿霉素脂质体、白蛋白结合型紫杉醇等）治疗效果的解决方案更为实际。现代先进医学技术与纳米医学相结合用于治疗各种恶性肿瘤已受到越来越多的关注。最近，我们发现高压氧（HBO）疗法可以增强多柔比星脂质体的抗肿瘤疗效。受这项研究的启发，我们进一步开展了HBO疗法与其他纳米医学联合用于各种癌症治疗的研究，并发现HBO疗法可以显著提高纳米医学介导的光动力疗法和光热疗法在包括肝细胞癌、乳腺癌和神经胶质瘤在内的不同种类肿瘤中的抗肿瘤疗效。我们的结果表明，HBO疗法可能是提高纳米医学对缺氧实体恶性肿瘤治疗效果的一种通用策略。
