摘要
基于罗丹明的良好荧光性能,经化学偶联反应制备并表征了一个偶氮乏氧特异响应的“Off-On”型荧光成像探针(FY-4).从分子层面证实了其荧光“Off-On”性能和响应机制;在L02正常细胞及4T1,HeLa和A549肿瘤细胞层面考察了其对受试细胞株的毒性和不同乏氧时间的荧光成像性能;再利用4T1肿瘤模型,分别以肿瘤原位注射和尾静脉注射的方式考察了其荧光成像性能,并探究了其荧光成像介导切除肿瘤性能,最后还考察了FY-4的生物安全性.结果表明,FY-4有高的肿瘤乏氧靶向特异“关-开”响应的荧光成像差异显影及荧光成像介导切除肿瘤的潜能,结合其良好的光物理性能、生物安全性和明晰的给药时间等特性,有望为生物医学荧光成像介导肿瘤切除提供新的研究工具.
Determination of tumor boundary during surgery has a great significance to achieving precise resec⁃tion.The level of tumor hypoxia is closely related to the local concentration of reducing substances such as azo⁃benzene reductases(azoreductases,AzoR,an important class of biocatalysts in solid tumor),AzoR is able to reduce the nitrogen double bond(-N=N-)of azobenzene compounds to generate anilines.Therefore,the characterization might serve as optical AzoR probe during image-guided surgery,which exhibits wide range of application prospects in biomedicine field.In order to obtain a probe for tumor hypoxia fluorescence image-guided surgery with good targeting,low toxicity,good biocompatibility and high specificity,based on the mo⁃lecular cleavage of azobenzene induced by azoreductase hypoxia and the good fluorescence performance of rho⁃damine,an“Off-On”type tumor with a specific response to near-infrared azohypoxia was prepared and charac⁃terized by chemical coupling.Then we confirmed its fluorescence“Off-On”performance and response mecha⁃nism from the molecular level;at the level of L02,4T1,HeLa,and A549 tumor cells,the toxicity of the tested cell lines and the imaging performance on different hypoxia periods was also investigated.Next,4T1 tumor model was further constructed,and the performance of tumor in situ injection and tail vein injection fluo⁃rescence imaging were studied respectively.Furthermore,the performance of fluorescence imaging-mediated surgery of tumors was further explored.On this basis,the biological safety performance was investigated.The results show that this rhodamine azo probe has high target-specific tumor hypoxia responsiveness and excellent fluorescence imaging-mediated tumor surgery potential,combined with its good photophysical properties,con⁃trolled administration time,and biological security,which is expected to provide new research tools for bio⁃medical fluorescence imaging-mediated tumor resection.
作者
王萌萌
栾天骄
杨铭焱
吕佳佳
高杰
李洪玉
卫钢
袁泽利
WANG Mengmeng;LUAN Tianjiao;YANG Mingyan;LYU Jiajia;GAO Jie;LI Hongyu;WEI Gang;YUAN Zeli(School of Pharmacy,Key Laboratory of Basic Pharmacology of Ministry of Education,Key Laboratory of Biocatalysis&Chiral Drug Synthesis of Guizhou Province,International Joint Laboratory of Characteristic Ethnic Medicine of the Ministry of Education,Guizhou International Scientific and Technological Cooperation Base for Medical Photo-Theranostics Technology and Innovative Drug Development,Zunyi Medical University,Zunyi 563000,China;Commonwealth Scientific and Industrial Research Organisation(CSIRO)Manufacturing,NSW2070,Australia)
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2021年第10期3071-3081,共11页
Chemical Journal of Chinese Universities
基金
国家自然科学基金(批准号:81660575,82060626)
贵州省创新群体重大项目(批准号:KY[2018]024)
遵义医科大学学术新苗项目(批准号:[2017]5733-042)
遵义医科大学博士启动基金(批准号:F-862)
贵州省科技支撑计划(批准号:黔科合支撑[2020]4Y158号)
贵州省科技厅平台项目(批准号:[2020]4104号)资助.
关键词
乏氧探针
偶氮还原酶
荧光成像
罗丹明衍生物
成像介导肿瘤切除
Hypoxia probe
Azoreductase
Fluorescence image
Rhodamine derivatives
Imaging-mediated tumor resection
作者简介
联系人:袁泽利,男,博士,教授,主要从事医用光学诊疗技术与创新药物研究.E-mail:zlyuan2002@126.com。
