Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University , Suzhou 215123, China.
School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University , Suzhou, Jiangsu 21513, China.
Nano Lett. 2016 Oct 12;16(10):6145-6153. doi: 10.1021/acs.nanolett.6b02365. Epub 2016 Sep 14.
Tumor hypoxia is known to be one of critical reasons that limit the efficacy of cancer therapies, particularly photodynamic therapy (PDT) and radiotherapy (RT) in which oxygen is needed in the process of cancer cell destruction. Herein, taking advantages of the great biocompatibility and high oxygen dissolving ability of perfluorocarbon (PFC), we develop an innovative strategy to modulate the tumor hypoxic microenvironment using nano-PFC as an oxygen shuttle for ultrasound triggered tumor-specific delivery of oxygen. In our experiment, nanodroplets of PFC stabilized by albumin are intravenously injected into tumor-bearing mice under hyperoxic breathing. With a low-power clinically adapted ultrasound transducer applied on their tumor, PFC nanodroplets that adsorb oxygen in the lung would rapidly release oxygen in the tumor under ultrasound stimulation, and then circulate back into the lung for reoxygenation. Such repeated cycles would result in dramatically enhanced tumor oxygenation and thus remarkably improved therapeutic outcomes in both PDT and RT treatment of tumors. Importantly, our strategy may be applied for different types of tumor models. Hence, this work presents a simple strategy to promote tumor oxygenation with great efficiency using agents and instruments readily available in the clinic, so as to overcome the hypoxia-associated resistance in cancer treatment.
肿瘤缺氧是限制癌症治疗效果的关键原因之一，特别是在光动力疗法（PDT）和放射疗法（RT）中，癌症细胞的破坏过程需要氧气。在此，我们利用全氟碳化物（PFC）的优异生物相容性和高氧气溶解能力，开发了一种创新策略，通过纳米 PFC 作为氧气穿梭物，调节肿瘤缺氧微环境，实现超声触发的肿瘤特异性氧气输送。在我们的实验中，白蛋白稳定的 PFC 纳米液滴在高氧呼吸下被静脉注射到荷瘤小鼠体内。应用低功率临床适应超声换能器于肿瘤上，在超声刺激下，在肺部吸附氧气的 PFC 纳米液滴会迅速在肿瘤中释放氧气，然后循环回到肺部进行再氧合。这种反复循环会导致肿瘤氧合显著增强，从而显著改善 PDT 和 RT 治疗肿瘤的效果。重要的是，我们的策略可应用于不同类型的肿瘤模型。因此，本工作提出了一种利用临床中易得的试剂和仪器高效促进肿瘤氧合的简单策略，以克服癌症治疗中与缺氧相关的耐药性。
