Bioengineering Graduate Program, Department of Chemical and Biological Engineering , The Hong Kong University of Science and Technology , Hong Kong , China.
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences , Shenzhen 518055 , China.
ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36805-36813. doi: 10.1021/acsami.8b15293. Epub 2018 Oct 19.
Hypoxia in solid tumors may be a hindrance to effective treatments of tumors in achieving their therapeutic potential, especially for photodynamic therapy (PDT) which requires oxygen as the supplement substrate. Oxygen delivery using perfluorocarbon emulsions or lipid oxygen microbubbles has been developed as the agents to supply endogenous oxygen to fuel singlet oxygen generation in PDT. However, such methods suffer from premature oxygen release and storage issues. To address these limitations, we designed lipid-polymer bilaminar oxygen nanobubbles with chlorin e6 (Ce6) conjugated to the polymer shell as a novel oxygen self-supplement agent for PDT. The resultant nanobubbles possessed excellent stability to reduce the risk of premature oxygen release and were stored as freeze-dried powders to avoid shelf storage issues. In vitro and in vivo experimental results demonstrated that the nanobubbles exhibited much higher cellular uptake rates and tumor targeting efficiency compared to free Ce6. Using the oxygen nanobubbles for PDT, a significant enhancement of therapeutic efficacy and survival rates was achieved on a C6 glioma-bearing mice model with no noticeable side effects, owing to the greatly enhanced singlet oxygen generation powered by oxygen encapsulated nanobubbles.
肿瘤组织中的缺氧可能会阻碍肿瘤的有效治疗以发挥其治疗潜力，特别是对于需要氧作为补充底物的光动力疗法（PDT）。已经开发了使用全氟碳乳液或脂质氧微泡将氧输送到 PDT 中以提供内源性氧来为单线态氧的产生提供燃料的方法。然而，这些方法存在氧气过早释放和存储的问题。为了解决这些限制，我们设计了具有氯乙酮（Ce6）连接到聚合物壳的脂质-聚合物双层氧纳米气泡作为 PDT 的新型氧自补充剂。所得纳米气泡具有出色的稳定性，可降低过早释放氧气的风险，并被储存为冻干粉末以避免货架存储问题。体外和体内实验结果表明，与游离的 Ce6 相比，纳米气泡具有更高的细胞摄取率和肿瘤靶向效率。使用氧纳米气泡进行 PDT，在 C6 神经胶质瘤荷瘤小鼠模型中实现了治疗效果和存活率的显著提高，且没有明显的副作用，这主要得益于封装在纳米气泡中的氧大大增强了单线态氧的生成。
