一种聚集诱导发光光热剂用于骨肉瘤诊疗研究  

Aggregation-induced emission molecules with highly efficient fluorescence emission in the NIR-Ⅱfor photothermal diagnosis and therapy of osteosarcoma

作　　者：文巍 邓谢鹏 谢大路 陈向荣 李劲峰[1] 寇红伟[1] 刘宏建[1] 苏会芳 Wen Wei;Deng Xiepeng;Xie Dalu;Chen Xiangrong;Li Jinfeng;Kou Hongwei;Liu Hongjian;Su Huifang(Department of Orthopedics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院骨科医学部,郑州450052

出　　处：《中华实验外科杂志》2024年第2期325-327,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金委员(81902356、82072581、82272842、81972523);河南省科技厅省级科技研发计划联合基金(优势学科培育类)重点项目(222301420018);河南省高校科技创新人才支持计划(24HASTIT066);河南省优秀青年基金项目(232300421053);河南省中青年卫生健康科技创新人才(杰出青年)项目(YXKC2022032)。

摘　　要：目的探讨具有聚集诱导发光(AIE)性质的新型荧光分子(AIEgens)构建的纳米颗粒(2TT-oC6B NPs)的光热和荧光成像性能,以及其对骨肉瘤细胞的杀伤效果和体内肿瘤靶向能力。方法首先用不同功率(0.5、1.0和1.5 W/cm^(2))808 nm激光和不同浓度(0、25、50、100、200μmol/L)的2TT-oC6B NPs磷酸盐缓冲液(PBS)溶液进行体外光热性能检测,然后采用143B作为模型细胞,探讨其生物相容性和光热杀伤效果,最终用K7M2细胞接种在BALB/c小鼠皮下,构建小鼠肿瘤模型,通过尾静脉注射2TT-oC6B NPs 5 mg/kg检测其体内肿瘤靶向能力。采用t检验确定实验组与对照组之间的显着性。结果与对照组比较,2TT-oC6B NPs在808 nm激光照射下最高温度可升至约70℃并具有近红外二区发光成像能力;CCK-8实验表明,与对照组143B细胞存活率比较,100μmol/L时143B细胞存活率不受影响(t=1.734,P>0.05),差异无统计学意义,表现出其良好的生物相容性。而经过808 nm激光照射后143B细胞存活率显著下降(t=15.01,P<0.05),表现出其优异的光热杀伤效果;同时活/死细胞染色更直接的呈现了这一结果;小鼠体内肿瘤成像结果表明其能在30 min内就富集在肿瘤部位并长时间保留。结论2TT-oC6B NPs具有优异的光热转换性能和荧光成像能力,其本身具有良好地生物相容性,而当在808 nm激光照射下展现出高效的光热杀伤效果。同时它能迅速靶向肿瘤,并在瘤内长期富集,这表明其可能作为骨肿瘤外科手术切除的一种良好辅助治疗方式,是一个性能优异的骨肉瘤诊疗一体化探针。Objective To explore the photothermal and fluorescence imaging properties of nanoparticles(2TT-oC6B NPs)constructed by novel fluorescent molecules(AIEgens)with aggregation-induced emission(AIE)properties,as well as their killing effect on osteosarcoma and in vivo tumor-targeting ability.Methods First,the in vitro photothermal properties were examined using 808 nm lasers with different powers(0.5,1.0 and 1.5 W/cm^(2))and different concentrations(0,25,50,100 and 200μmol/L)of 2TT-oC6B NPs phosphate buffer saline(PBS)solution,and then 143B cells were used as the model cells to explore its biocompatibility and photothermal killing effect,and finally K7M2 cells were used to inoculate the subcutaneous area of BALB/c mice to construct mice tumor models,and the in vivo tumor-targeting ability was examined by injecting 2TT-oC6B NPs(5 mg/kg)through the tail vein.Thet test was used to determine the significance between experimental and control groups.Results Compared with the control group,2TT-oC6B NPs could reach a maximum temperature of about 70℃and had Near-infrared-Ⅱ(NIR-Ⅱ)emission imaging ability under 808 nm laser irradiation.CCK-8 experiments showed that compared with the control group,the survival rate of 143B cells at 100μmol/L was not affected(t=1.734,P>0.05),demonstrating its good biocompatibility.The survival rate of 143B cells was significantly decreased after 808 nm laser irradiation(t=15.01,P<0.05),demonstrating its excellent photothermal killing effect.Meanwhile,the live/dead cell staining showed this result more directly.In vivo tumor imaging in mice demonstrated that it could be enriched at the tumor site within 30 min and retained in the tumor for a long time.Conclusion 2TT-oC6B NPs have excellent photothermal conversion performance and fluorescence imaging capability.It has good biocompatibility,while it shows efficient photothermal killing effect when under 808 nm laser irradiation.At the same time,its ability to rapidly target tumors and long-term intratumoral enrichment suggests that it may ser

关 键 词：光热治疗 骨肉瘤 

分 类 号：R738.1[医药卫生—肿瘤]