Liposomes co-loaded with metformin and chlorin e6 modulate tumor hypoxia during enhanced photodynamic therapy  

作　　者：Xuejiao Song Liangzhu Feng Chao Liang Min Gao Guosheng Song Zhuang Liu 

机构地区：[1]Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China

出　　处：《Nano Research》2017年第4期1200-1212,共13页纳米研究（英文版）

基　　金：Acknowledgements This work was partially supported by the National Basic Research Program of China （973 Program） （No. 2012CB932600）, the National Natural Science Foundation of China （Nos. 51525203 and 51132006）, a Jiangsu Natural Science Fund for Distinguished Young Scholars （No. BK20130005）, Collaborative Innovation Center of Suzhou Nano Science and Technology, and a Project Funded by the Priority Academic Program Development （PAPD） of Jiangsu Higher Education Institutions.

摘　　要：Though photodynamic therapy （PDT） has been widely used in the non-invasive destruction of solid tumors, the therapeutic efficacy of PDT is often limited by the hypoxic tumor environment. Herein, we report the innovative use of metformin, an oral hypoglycemic agent commonly used in the treatment of type II diabetes, to improve tumor oxygenation, and overcome tumor hypoxia-associated resistance to PDT. In our design, hydrophilic metformin and modified hydrophobic chlorin e6 （HCe6） are co-encapsulated within the inner cavity and outer membrane of liposomes, respectively. Due to the high uptake of liposome nanoparticles by tumors, and the sustained release of metformin, the intravenous administration of metformin （Met）-HCe6-Liposome nanoparticles greatly improves tumor oxygena- tion in several different tumor models, as revealed by in vivo photoacoustic imaging and ex vivo immunofluorescence staining. Systemic administration of Met-HCe6-Liposomes followed by in vivo PDT achieved significantly improved therapeutic effects compared to that of PDT without metformin. Hence, our study represents a new strategy for the improvement of PDT efficacy through the modulation of tumor oxygenation by clinically approved agents.Though photodynamic therapy （PDT） has been widely used in the non-invasive destruction of solid tumors, the therapeutic efficacy of PDT is often limited by the hypoxic tumor environment. Herein, we report the innovative use of metformin, an oral hypoglycemic agent commonly used in the treatment of type II diabetes, to improve tumor oxygenation, and overcome tumor hypoxia-associated resistance to PDT. In our design, hydrophilic metformin and modified hydrophobic chlorin e6 （HCe6） are co-encapsulated within the inner cavity and outer membrane of liposomes, respectively. Due to the high uptake of liposome nanoparticles by tumors, and the sustained release of metformin, the intravenous administration of metformin （Met）-HCe6-Liposome nanoparticles greatly improves tumor oxygena- tion in several different tumor models, as revealed by in vivo photoacoustic imaging and ex vivo immunofluorescence staining. Systemic administration of Met-HCe6-Liposomes followed by in vivo PDT achieved significantly improved therapeutic effects compared to that of PDT without metformin. Hence, our study represents a new strategy for the improvement of PDT efficacy through the modulation of tumor oxygenation by clinically approved agents.

关 键 词：photodynamic therapy liposomes metforrnin tumor hypoxia 

分 类 号：O[理学]