Theranostics 2018; 8(18):4898-4911. doi:10.7150/thno.27598
Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles
1. State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & School of Life Sciences, Nanjing University, Nanjing 210093, China
2. Institute of Drug R&D, Nanjing University, Nanjing 210093, China
3. Jiangsu Provincial Key Laboratory for Nano Technology, Nanjing University, Nanjing 210093, China
Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles.
Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition. To evaluate the effect of PFC nanoparticles on radiation sensitization, CT26 tumor and SUM49PT tumor model were used.
Results: In this study, PFC was encapsulated into albumin and intravenously injected into tumor-bearing mice without hyperoxic breathing. After accumulation in the tumor, PFC nanoparticles rapidly released the oxygen that was physically dissolved in PFC as the first-stage of oxygen delivery. Then, PFC subsequently promoted red blood cell infiltration, which further released O2 as the second-stage of oxygen delivery.
Conclusion: The hypoxic tumor microenvironment was rapidly relieved via two-stage oxygen delivery, effectively increasing radiotherapy efficacy. The safety of all substances used in this study has been clinically demonstrated, ensuring that this simple strategy could be rapidly and easily translated into clinical applications to solve the clinical problems associated with tumor hypoxia.
Keywords: perfluorocarbon nanoparticles, tumor hypoxia, two-stage oxygen delivery, radiotherapy
Zhou Z, Zhang B, Wang H, Yuan A, Hu Y, Wu J. Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles. Theranostics 2018; 8(18):4898-4911. doi:10.7150/thno.27598. Available from http://www.thno.org/v08p4898.htm