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 innova...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.展开更多
文摘目的 探讨西格列汀联合二甲双胍治疗初发2型糖尿病的效果。方法 选取2014年12月-2015年12月在我院住院的40例新诊断2型糖尿病患者作为研究对象,随机分为对照组和观察组,各20例。对照组采用二甲双胍治疗,观察组采用西格列汀联合二甲双胍治疗。比较两组治疗前后的空腹血糖（FBG）、餐后2 h血糖（2 h PG）、糖化血红蛋白（Hb A1c）、体质量指数（BMI）、空腹胰岛素（FINs）、胰岛素抵抗指数（HOMA-IR）等指标的变化以及不良反应发生率。结果 两组治疗12周后的FBG、2 h PG、Hb A1c、BMI水平低于治疗前,FINs水平高于治疗前,差异有统计学意义（P〈0.05）。观察组治疗12周后的FBG、2 h PG、Hb A1c、BMI水平低于对照组,FINs水平高于对照组治疗后,差异有统计学意义（P〈0.05）。两组的不良反应发生率比较,差异无统计学意义（P〉0.05）。结论 磷酸西格列汀联合二甲双胍治疗初发2型糖尿病较二甲双胍单药治疗具有更好的控制血糖效果。
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.
文摘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.
