生物打印HepG2细胞用于二氢卟酚e6的声动力抗癌活性研究  

Bioprinted HepG2 cells for studying sonodynamic anticancer activity of chlorine e6

作　　者：李晓瑞 邓权锋 罗勇[1] 林炳承[3] 赵伟杰[1] 张秀莉 LI Xiao-rui;DENG Quan-feng;LUO Yong;LIN Bing-cheng;ZHAO Wei-jie;ZHANG Xiu-li(Dalian University of Technology,Dalian 116024,China;Soochow University,Suzhou 215123,China;Dalian Institute of Chemical Physics,Chinese Academy of Science,Dalian 116023,China)

机构地区：[1]大连理工大学,辽宁大连116024 [2]苏州大学,江苏苏州215123 [3]中国科学院大连化学物理研究所,辽宁大连116023

出　　处：《药学学报》2020年第12期2976-2981,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(21675017);国家重点研究开发计划项目(2017YFC1702001).

摘　　要：本研究利用生物打印技术构建了HepG2三维肿瘤组织用于声敏药物二氢卟酚e6(chlorine e6,Ce6)的声动力抗癌活性研究。以海藻酸/明胶/羟乙基纤维素的复合生物材料作为生物墨水,3D打印了HepG2肿瘤细胞,Live-Dead试剂盒检测细胞存活率,MTT法检测细胞增殖情况,考察打印后细胞活力。自主搭建了微型超声装置,利用声能转换热能引起的温度改变,估算装置不同功率下的超声强度。14.3和28.6μg·mL^(-1)的Ce6作用于二维培养和三维打印的HepG2细胞,以0.15 W·cm^(2)的超声强度作用60 s,MTT法检测Ce6的抗肿瘤活性。结果显示,打印的HepG2细胞活性高达95%,培养7天开始形成肿瘤微球。装置最大超声强度低于3 W·cm^(2),对正常肝细胞LO2无损伤。通过比较Ce6对2D培养和打印的HepG2细胞抗癌活性大小,发现三维HepG2肿瘤的Ce6声动力抗癌活性较2D培养降低了63.4%,显示了三维肿瘤的耐声敏药性,为声动力疗法体外三维肿瘤模型的发展提供了可能性。This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6(Ce6).HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation.The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy.Ce6 of 14.3 and 28.6μg·mL^(-1) were acted on two-dimensional cultured and three-dimensional printed HepG2 cells,and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15W·cm^(2)for 60 s.The results showed that the activities of bioprinted HepG2 cells were as high as 95%,and tumor microspheres were formed after 7 days of culture.The ultrasound intensity was lower than 3 W·cm^(2),which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells.By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells,it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4%lower than that on 2D culture cells,indicating the acoustic drug resistance of three-dimensional tumor model.Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.

关 键 词：生物打印 生物相容性材料 肝肿瘤 抗肿瘤药 超声疗法 

分 类 号：R943[医药卫生—药剂学]