Rong Xiao, Xiang Xi, Zhao Yicheng, Qiu Li, DU Fangxue
（ 610041） Department of Ultrasound Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Sep 20;55(5):1159-1165. doi: 10.12182/20240960108.
To study the role of curcumin-mediated sonodynamic therapy in the treatment of malignant melanoma, and to provide a new strategy for the treatment of malignant melanoma.
The ultrasonic sound and vibration method was applied to coat curcumin with mouse melanoma cell membrane, thereby forming biomimetic curcumin. The morphology of biomimetic curcumin was observed by transmission electron microscope. Flow cytometry was used to analyze the effect of biomimetic curcumin in terms of targeting, apoptosis, and intracellular reactive oxygen species (ROS) production. The experiment was divided into control group, US group, turmeric group, imitation turmeric group, and imitation turmeric+US group, with 3 mice in each group. The safety of biomimetic curcumin was evaluated by HE staining. In addition, HE, CD31, Ki67, and TUNEL stainings were performed to evaluate the anti-melanoma therapeutic effect of ultrasound combined with biomimetic curcumin.
The biomimetic curcumin had a generally uniform morphology and possessed a core-shell structure. Flow cytometry analysis performed with FlowJo showed that the biomimetic curcumin could be effectively taken up by melanoma cells. The apoptosis rate was (10.30±0.61)% in the control group, (10.41±3.13)% in the ultrasound group, (24.97±1.38)% in the curcumin group, (31.39±3.84)% in the biomimetic curcumin group, and (40.89±0.79)% in the biomimetic curcumin and ultrasound combination group. The apoptosis rate in the biomimetic curcumin and ultrasound combination group was higher than those in the other groups (<0.05). The results of ROS flow cytometry showed that, compared with the control group, the ultrasound group demonstrated almost no increase in the fluorescence intensity, while the other groups showed an increase in the fluorescence intensity to varying degrees. There was no significant difference in the fluorescence intensity between the biomimetic curcumin group ([1.10±0.38]%) and the curcumin group ([0.73±0.26]%) (>0.05). The fluorescence intensity of the biomimetic curcumin and ultrasound combination group ([3.35±0.04]%) was higher than those of the other groups (<0.05). HE staining showed no obvious abnormalities in the morphology of heart, liver, spleen, lung, and kidney tissues in any of the treatment groups. HE staining showed the most significant changes in cell morphology in the biomimetic curcumin and ultrasound combination group, followed by the biomimetic curcumin group and the curcumin group. No obvious abnormalities in tumor cell morphology were observed in the ultrasound group. According to the respective results of CD31 staining, Ki67 staining, and TUNEL staining, the biomimetic curcumin and ultrasound combination group had the largest brown area, the highest number of red fluorescence, and the highest number of green fluorescence, followed by the biomimetic curcumin group and the curcumin group.
The biomimetic curcumin displays uniform morphology, a core-shell structure, and good targeting properties. When it is used in combination with ultrasound, biomimetic curcumin demonstrates a good anti-tumor therapeutic effect both and .
研究姜黄素介导的声动力疗法在恶性黑色素瘤治疗中的作用，为恶性黑色素瘤的治疗提供新策略。
采用超声声振法将姜黄素包裹于小鼠黑色素瘤细胞膜上，从而形成仿生姜黄素。通过透射电子显微镜观察仿生姜黄素的形态。运用流式细胞术分析仿生姜黄素在靶向性、凋亡及细胞内活性氧（ROS）产生方面的作用。实验分为对照组、超声组、姜黄组、仿姜黄组及仿姜黄+超声组，每组3只小鼠。通过苏木精-伊红（HE）染色评估仿生姜黄素的安全性。此外，进行HE、CD31、Ki67及TUNEL染色以评估超声联合仿生姜黄素的抗黑色素瘤治疗效果。
仿生姜黄素形态总体均匀，具有核壳结构。使用FlowJo进行的流式细胞术分析表明，仿生姜黄素可被黑色素瘤细胞有效摄取。对照组凋亡率为（10.30±0.61）%，超声组为（10.41±3.13）%，姜黄素组为（24.97±1.38）%，仿生姜黄素组为（31.39±3.84）%，仿生姜黄素与超声联合组为（40.89±0.79）%。仿生姜黄素与超声联合组的凋亡率高于其他组（<0.05）。ROS流式细胞术结果显示，与对照组相比，超声组荧光强度几乎无增加，而其他组荧光强度有不同程度增加。仿生姜黄素组（[1.10±0.38]%）与姜黄素组（[0.73±0.26]%）的荧光强度无显著差异（>0.05）。仿生姜黄素与超声联合组的荧光强度（[3.35±0.04]%）高于其他组（<0.05）。HE染色显示，各治疗组心脏、肝脏、脾脏、肺脏及肾脏组织形态均无明显异常。HE染色显示，仿生姜黄素与超声联合组细胞形态变化最显著，其次为仿生姜黄素组和姜黄素组。超声组肿瘤细胞形态未见明显异常。根据CD31染色、Ki67染色及TUNEL染色各自的结果，仿生姜黄素与超声联合组棕色面积最大，红色荧光数量最多，绿色荧光数量最多，其次为仿生姜黄素组和姜黄素组。
仿生姜黄素形态均匀，具有核壳结构，靶向性良好。与超声联合使用时，仿生姜黄素在体内外均表现出良好的抗肿瘤治疗效果。
