季铵化卟啉光敏剂的合成与细胞毒性评价  

Synthesis of quaternary ammonium porphyrin photosensitizer and the evaluation of its cytotoxicity

作　　者：刘书杰 曹洁 钱涛 肖刚 陈维国[1,2] 崔志华[1,2,5] LIU Shujie;CAO Jie;QIAN Tao;XIAO Gang;CHEN Weiguo;CUI Zhihua(Engineering Research Center for Eco-Dyeing&Finishing of Textiles,Ministry of Education,Zhejiang Sci-Tech University,Hangzhou 310018 China;Key Laboratory of Advanced Textile Materials and Manufacturing Technology,Ministry of Education,Zhejiang Sci-Tech University,Hangzhou 310018 China;Hangzhou Jihua Polymer Material Co.,Ltd..,Hangzhou311228,China;Jinhua Shuanghong Chemical Co.,Ltd..,Jin hua321000,China;Shangyu Industrial Technology Research Institute Co.,Ltd.,Zhejiang Sci-Tech University,Shaoxing 312300,China)

机构地区：[1]浙江理工大学生态染整技术教育部工程研究中心,杭州310018 [2]浙江理工大学先进纺织材料与制备技术教育部重点实验室,杭州310018 [3]杭州吉华高分子材料股份有限公司,杭州311228 [4]金华双宏化工有限公司,浙江金华321000 [5]浙江理工大学上虞工业技术研究院有限公司,浙江绍兴312300

出　　处：《浙江理工大学学报（自然科学版）》2022年第4期556-564,共9页Journal of Zhejiang Sci-Tech University(Natural Sciences)

基　　金：国家自然科学基金项目(21808210);浙江省重点研发计划项目(2021C01058);浙江省自然科学基金项目(LY21B060010);金华市科技计划项目(2019-1-034)。

摘　　要：间四苯基卟啉(TPP)溶解性较差,导致其在光动力治疗中生物利用率低,且季铵化后对细胞的生长存在一定毒性,为解决该问题,合成了以六碳脂肪链为桥基、以共价键连接的新型季铵化卟啉光敏剂(QTPP),通过质谱、核磁共振氢谱对其结构进行表征,紫外-可见吸收光谱对其进行理化性质测试,并采用动态光散色仪、透射电子显微镜、Zeta电位仪对两亲性脂质体(Dspe-PEG_(2000))包覆QTPP形成的脂质体纳米粒子的(QTPP@Dspe-PEG_(2000))分散液进行测量与分析,进一步测试了无光照条件下QTPP和QTPP@Dspe-PEG_(2000)对人正常乳腺MCF-10A细胞的毒性以及光照条件下QTPP@Dspe-PEG_(2000)对小鼠乳腺癌细胞(4T1)的毒性。结果表明:QTPP在甲醇中的溶解性较好,QTPP@Dspe-PEG_(2000)分散液具有良好的稳定性,平均粒径为98 nm,表面形貌为规则球形,Zeta电位为-17.25 mV。无光照条件下QTPP对人正常乳腺MCF-10A细胞的毒性较大,而QTPP@Dspe-PEG_(2000)对正常乳腺MCF-10A细胞的毒性较低,但在光照条件下QTPP@Dspe-PEG_(2000)对小鼠4T1细胞表现出较强杀伤效果。上述结果表明,TPP经过季铵化后溶解性得到有效提高,用两亲性脂质体Dspe-PEG_(2000)对QTPP进行包覆可以有效降低QTPP对健康细胞的毒性,表明QTPP在光动力治疗方面具有应用前景。In order to solve the problems of low bioavailability of tetraphenylporphyrin(TPP)in photodynamic therapy due to its poor solubility and its toxicity to cell growth after quaternization,a new quaternized porphyrin photosensitizer(QTPP)with six carbon fat chain as bridge connected by covalent bond was synthesized in this paper.Its structure was characterized by mass spectrometry and nuclear magnetic resonance,and its physical and chemical properties were tested by UV-VIS absorption spectrum.The amphipathic dispersion liquid(QTPP@Dspe-PEG_(2000))of liposome nanoparticles formed by amphiphilic liposomes(Dspe-PEG_(2000))coated with QTPP were characterized by dynamic light dispersive colorimeter,transmission electron microscope and zeta potentiometer was measured and analyzed.The toxicity of QTPP and QTPP@Dspe-PEG_(2000) to human normal breast MCF-10 A cells under dark conditions and the toxicity of QTPP@Dspe-PEG_(2000) to mouse 4 T1 cells under light conditions were further tested.The results showed that the solubility of QTPP in methanol was good and QTPP@Dspe-PEG_(2000) dispersion liquid exhibited good stability.The average particle size was 98 nm,the surface morphology was regular spherical,and the zeta potential was-17.25 mV.QTPP had stronger toxicity to human normal breast MCF-10 A cells under dark conditions,while QTPP@Dspe-PEG_(2000) had low toxicity to normal breast MCF-10 A cells,but QTPP@Dspe-PEG_(2000) showed a strong killing effect on mouse 4 T1 cells under light conditions.The above results show that the solubility of TPP has been effectively improved after quaternization.Coating QTPP with amphiphilic liposome Dspe-PEG_(2000) can effectively reduce the toxicity of QTPP to healthy cells,indicating that QTPP has potential application prospects in photodynamic therapy.

关 键 词：光动力治疗 光敏剂 四苯基卟啉 季铵化 纳米级颗粒 单线态氧 

分 类 号：R318.08[医药卫生—生物医学工程]