(Correspondent Liu Xin) On July 15th, a research paper entitled "Hyperbaric oxygen regulates tumor microenvironment and boosts commercialized nanomedicine delivery for potent eradication of cancer stem-like cells " has been published on Nano Today (IF = 20.7), which reported a novel strategy to selectively promote nanomedicine delivery efficiency by hyperbaric oxygen for potent elimination of cancer stem cells. This work is contributed by the team of Prof. Zifu Li and Prof. Xiangliang Yang from College of Life Science & Technology and National Engineering Research Center for Nanomedicine, HUST.
Cancer stem cells (CSCs) are the main culprits that induce tumor genesis, development, metastasis and recurrence, so the eradication of CSCs is of great significance for cancer therapy. However, CSCs are usually located in the central region of tumor, far away from tumor blood vessels, making it difficult for nanomedicine to extravasate from blood vessels and penetrate through tumor extracellular matrix to kill cancer stem cells. To date, there is few effective means to improve the delivery efficiency of commercialized nanomedicine. Therefore, it is urgently needed to improve the delivery efficiency of commercialized nanomedicine for eradication of cancer stem cells and enhancing the anti-tumor efficacy of commercialized nanomedicine.
Prof. Xiangliang Yang’s team proposed Five Features Principle for the design of tumor-targeted nanomedicine, which contain long circulation, tumor accumulation, deep penetration, cellular internalization and drug release. Based on the Five Features Principle, Prof. Xiangliang Yang’s team optimized the dynamics of nanomedicine in vivo by regulating physical and chemical properties of nanomedicine including size, zeta potential, hydrophilicity, surface charge, to name a few. All the nanomedicine designed according to Five Features Principle has achieved augmented antitumor efficiency and negligible side effects. However, these rational designed multifunctional nanomedicines are still in the laboratory stage, whereas their safety, response rate and routes of industrial production still need to be further studied. Therefore, it is urgent to seek more reliable and universal means to improve the delivery efficiency of commercialized nanomedicine.
Based on the background mentioned above, in this study, hyperbaric oxygen (HBO) was used to promote nanomedicine delivery efficiency by regulating tumor mechanical microenvironment, so as to effectively eradicate cancer stem cells and enhance the anti-tumor efficacy. First of all, HBO regulated tumor mechanical microenvironment by reducing extracellular matrix density and solid stress. HBO also modulated tumor vascular microenvironment by normalizing both structure and function of blood vessels within tumors. Accordingly, compared with the free drugs which cannot be effectively accumulated in the tumor site, HBO selectively enabled nanomedicine to achieve superior tumor accumulation, deep penetration and cellular internalization. Secondly, as hypoxia can induce the generation of cancer stem cells, HBO was used in this study to alleviate tumor hypoxia and directly reduce the stemness and self-renewal ability of CSCs. Moreover, HBO relieved the cell cycle arrest of CSCs, which sensitized CSCs to nanomedicine and further enhanced the eradication efficiency. On the basis of two mechanisms, this study further verified the effectiveness and safety of the combination therapy through lung metastasis, breast orthotopic and pancreatic orthotopic tumor models. Results showed that HBO significantly enhanced the eradication of CSCs, inhibited tumor metastasis, and finally achieved augmented antitumor efficacy.
This study proposed a universal strategy to promote the delivery efficiency of nanomedicine, which will be beneficial to marketed nanomedicines. As HBO is potent in reducing the tumor stemness by alleviating hypoxia, HBO also has great significance for cancer stem cell research.
Post-doctor fellow Xin Liu, master student Ningbing Ye from College of Life Science & Technology, HUST contributed equally to this work. Undergraduate student Yihan Deng, majored in biopharmaceutics and nanomedicine, participated in this work. This work was financially supported by grants from the National Key Research and Development Program of China (2020YFA0211200, 2020YFA0710700, and 2018YFA0208900), the National Science Foundation of China (31972927), the Scientific Research Foundation of HUST (3004170130), the Program for HUST Academic Frontier Youth Team (2018QYTD01), and the HCP Program for HUST.
Article Link: https://doi.org/10.1016/j.nantod.2021.101248
